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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

General Review Article

Sepsis: From Historical Aspects to Novel Vistas. Pathogenic and Therapeutic Considerations

Author(s): Thea Magrone* and Emilio Jirillo

Volume 19, Issue 4, 2019

Page: [490 - 502] Pages: 13

DOI: 10.2174/1871530319666181129112708

Price: $65

Abstract

Background: Sepsis is a clinical condition due to an infectious event which leads to an early hyper-inflammatory phase followed by a status of tolerance or immune paralysis. Hyper-inflammation derives from a massive activation of immune (neutrophils, monocytes/macrophages, dendritic cells and lymphocytes) and non-immune cells (platelets and endothelial cells) in response to Gram-negative and Gram-positive bacteria and fungi.

Discussion: A storm of pro-inflammatory cytokines and reactive oxygen species accounts for the systemic inflammatory response syndrome. In this phase, bacterial clearance may be associated with a severe organ failure development. Tolerance or compensatory anti-inflammatory response syndrome (CARS) depends on the production of anti-inflammatory mediators, such as interleukin-10, secreted by T regulatory cells. However, once triggered, CARS, if prolonged, may also be detrimental to the host, thus reducing bacterial clearance.

Conclusion: In this review, the description of pathogenic mechanisms of sepsis is propaedeutic to the illustration of novel therapeutic attempts for the prevention or attenuation of experimental sepsis as well as of clinical trials. In this direction, inhibitors of NF-κB pathway, cell therapy and use of dietary products in sepsis will be described in detail.

Keywords: Bacteria, cytokines, fungi, inflammation, therapy, tolerance, sepsis.

Graphical Abstract
[1]
Bone, R.C.; Balk, R.A.; Cerra, F.B.; Dellinger, R.P.; Fein, A.M.; Knaus, W.A.; Schein, R.M.; Sibbald, W.J. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest, 1992, 101(6), 1644-1655.
[2]
Martin, G.S.; Mannino, D.M.; Eaton, S.; Moss, M. The epidemiology of sepsis in the United States from 1979 through 2000. N. Engl. J. Med., 2003, 348(16), 1546-1554.
[3]
Caradonna, L.; Amati, L.; Magrone, T.; Pellegrino, N.M.; Jirillo, E.; Caccavo, D. Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. J. Endotoxin Res., 2000, 6(3), 205-214.
[4]
Caradonna, L.; Amati, L.; Lella, P.; Jirillo, E.; Caccavo, D. Phagocytosis, killing, lymphocyte-mediated antibacterial activity, serum autoantibodies, and plasma endotoxins in inflammatory bowel disease. Am. J. Gastroenterol., 2000, 95(6), 1495-1502.
[5]
Jirillo, E.; Caccavo, D.; Magrone, T.; Piccigallo, E.; Amati, L.; Lembo, A.; Kalis, C.; Gumenscheimer, M. The role of the liver in the response to LPS: experimental and clinical findings. J. Endotoxin Res., 2002, 8(5), 319-327.
[6]
Caradonna, L.; Mastronardi, M.L.; Magrone, T.; Cozzolongo, R.; Cuppone, R.; Manghisi, O.G.; Caccavo, D.; Pellegrino, N.M.; Amoroso, A.; Jirillo, E.; Amati, L. Biological and clinical significance of endotoxemia in the course of hepatitis C virus infection. Curr. Pharm. Des., 2002, 8(11), 995-1005.
[7]
Magrone, T.; Jirillo, E. Disorders of innate immunity in human ageing and effects of nutraceutical administration. Endocr. Metab. Immune Disord. Drug Targets, 2014, 14(4), 272-282.
[8]
Singer, M.; Deutschman, C.S.; Seymour, C.W.; Shankar-Hari, M.; Annane, D.; Bauer, M.; Bellomo, R.; Bernard, G.R.; Chiche, J.D.; Coopersmith, C.M.; Hotchkiss, R.S.; Levy, M.M.; Marshall, J.C.; Martin, G.S.; Opal, S.M.; Rubenfeld, G.D.; van der Poll, T.; Vincent, J.L.; Angus, D.C. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 2016, 315(8), 801-810.
[9]
Levy, M.M.; Fink, M.P.; Marshall, J.C.; Abraham, E.; Angus, D.; Cook, D.; Cohen, J.; Opal, S.M.; Vincent, J.L.; Ramsay, G. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit. Care Med., 2003, 31(4), 1250-1256.
[10]
Kaukonen, K.M.; Bailey, M.; Pilcher, D.; Cooper, D.J.; Bellomo, R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N. Engl. J. Med., 2015, 372(17), 1629-1638.
[11]
Fujishima, S. Organ dysfunction as a new standard for defining sepsis. Inflamm. Regen., 2016, 36, 24.
[12]
Angus, D.C.; van der Poll, T. Severe sepsis and septic shock. N. Engl. J. Med., 2013, 369(9), 840-851.
[13]
Hattori, Y.; Hattori, K.; Suzuki, T.; Matsuda, N. Recent advances in the pathophysiology and molecular basis of sepsis-associated organ dysfunction: Novel therapeutic implications and challenges. Pharmacol. Ther., 2017, 177, 56-66.
[14]
van der Poll, T.; van de Veerdonk, F.L.; Scicluna, B.P.; Netea, M.G. The immunopathology of sepsis and potential therapeutic targets. Nat. Rev. Immunol., 2017, 17(7), 407-420.
[15]
Abraham, E. Nuclear factor-kappaB and its role in sepsis-associated organ failure. J. Infect. Dis., 2003, 187(Suppl. 2), S364-S369.
[16]
Ranieri, V.M.; Thompson, B.T.; Barie, P.S.; Dhainaut, J.F.; Douglas, I.S.; Finfer, S.; Gårdlund, B.; Marshall, J.C.; Rhodes, A.; Artigas, A.; Payen, D.; Tenhunen, J.; Al-Khalidi, H.R.; Thompson, V.; Janes, J.; Macias, W.L.; Vangerow, B.; Williams, M.D. Drotrecogin alfa (activated) in adults with septic shock. N. Engl. J. Med., 2012, 366(22), 2055-2064.
[17]
Opal, S.M.; Laterre, P.F.; Francois, B.; LaRosa, S.P.; Angus, D.C.; Mira, J.P.; Wittebole, X.; Dugernier, T.; Perrotin, D.; Tidswell, M.; Jauregui, L.; Krell, K.; Pachl, J.; Takahashi, T.; Peckelsen, C.; Cordasco, E.; Chang, C.S.; Oeyen, S.; Aikawa, N.; Maruyama, T.; Schein, R.; Kalil, A.C.; Van Nuffelen, M.; Lynn, M.; Rossignol, D.P.; Gogate, J.; Roberts, M.B.; Wheeler, J.L.; Vincent, J.L. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA, 2013, 309(11), 1154-1162.
[18]
Rittirsch, D.; Hoesel, L.M.; Ward, P.A. The disconnect between animal models of sepsis and human sepsis. J. Leukoc. Biol., 2007, 81(1), 137-143.
[19]
Raven, K. Rodent models of sepsis found shockingly lacking. Nat. Med., 2012, 18(7), 998.
[20]
Galanos, C.; Liideritz, O.; Rietschel, E.T.H.; Westphal, O. Newer aspects of the chemistry and biology of bacterial lipopolysaccarides, with special reference to their lipid A component. Int. Rev. Biochem., 1977, 14, 239-335.
[21]
Kagan, J.C. Lipopolysaccharide Detection across the Kingdoms of Life. Trends Immunol., 2017, 38(10), 696-704.
[22]
Moser, J.; Heeringa, P.; Jongman, R.M.; Zwiers, P.J.; Niemarkt, A.E.; Yan, R.; de Graaf, I.A.; Li, R.; Ravasz Regan, E.; Kümpers, P.; Aird, W.C.; van Nieuw Amerongen, G.P.; Zijlstra, J.G.; Molema, G.; van Meurs, M. Intracellular RIG-I signaling regulates TLR4-independent endothelial inflammatory responses to endotoxin. J. Immunol., 2016, 196(11), 4681-4691.
[23]
Baldwin, A.S., Jr The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu. Rev. Immunol., 1996, 14, 649-683.
[24]
Matsuda, N.; Hattori, Y. Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy. J. Pharmacol. Sci., 2006, 101(3), 189-198.
[25]
Aziz, M.; Jacob, A.; Yang, W.L.; Matsuda, A.; Wang, P. Current trends in inflammatory and immunomodulatory mediators in sepsis. J. Leukoc. Biol., 2013, 93(3), 329-342.
[26]
Magrone, T.; Jirillo, E. The impact of bacterial lipolysaccharides on the endothelial system: pathological consequences and therapeutic countermeasures. Endocr. Metab. Immune Disord. Drug Targets, 2011, 11(4), 310-325.
[27]
Hatherill, M.; Tibby, S.M.; Turner, C.; Ratnavel, N.; Murdoch, I.A. Procalcitonin and cytokine levels: Relationship to organ failure and mortality in pediatric septic shock. Crit. Care Med., 2000, 28(7), 2591-2594.
[28]
Marshall, J.C. Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome. Crit. Care Med., 2001, 29(Suppl. 7), S99-S106.
[29]
Mikacenic, C.; Hahn, W.O.; Price, B.L.; Harju-Baker, S.; Katz, R.; Kain, K.C.; Himmelfarb, J.; Liles, W.C.; Wurfel, M.M. Biomarkers of Endothelial Activation Are Associated with Poor Outcome in Critical Illness. PLoS One, 2015, 10(10), e0141251.
[30]
Venet, F.; Monneret, G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat. Rev. Nephrol., 2018, 14(2), 121-137.
[31]
Fallon, E.A.; Biron-Girard, B.M.; Chung, C.S.; Lomas-Neira, J.; Heffernan, D.S.; Monaghan, S.F.; Ayala, A. A novel role for coinhibitory receptors/checkpoint proteins in the immunopathology of sepsis. J. Leukoc. Biol., 2018. [Epub ahead of print].
[32]
Hotchkiss, R.S.; Monneret, G.; Payen, D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat. Rev. Immunol., 2013, 13(12), 862-874.
[33]
Munford, R.S.; Pugin, J. Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am. J. Respir. Crit. Care Med., 2001, 163(2), 316-321.
[34]
Schultz, M.J.; van der Poll, T. Animal and human models for sepsis. Ann. Med., 2002, 34(7-8), 573-581.
[35]
Steinhauser, M.L.; Hogaboam, C.M.; Kunkel, S.L.; Lukacs, N.W.; Strieter, R.M.; Standiford, T.J. IL-10 is a major mediator of sepsis-induced impairment in lung antibacterial host defense. J. Immunol., 1999, 162(1), 392-399.
[36]
Rossato, M.; Curtale, G.; Tamassia, N.; Castellucci, M.; Mori, L.; Gasperini, S.; Mariotti, B.; De Luca, M.; Mirolo, M.; Cassatella, M.A.; Locati, M.; Bazzoni, F. IL-10-induced microRNA-187 negatively regulates TNF-α, IL-6, and IL-12p40 production in TLR4-stimulated monocytes. Proc. Natl. Acad. Sci. USA, 2012, 109(45), E3101-E3110.
[37]
Sugimoto, K.; Galle, C.; Preiser, J.C.; Creteur, J.; Vincent, J.L.; Pradier, O. Monocyte CD40 expression in severe sepsis. Shock, 2003, 19(1), 24-27.
[38]
Sinistro, A.; Almerighi, C.; Ciaprini, C.; Natoli, S.; Sussarello, E.; Di Fino, S.; Calò-Carducci, F.; Rocchi, G.; Bergamini, A. Downregulation of CD40 ligand response in monocytes from sepsis patients. Clin. Vaccine Immunol., 2008, 15(12), 1851-1858.
[39]
Lissauer, M.E.; Johnson, S.B.; Bochicchio, G.V.; Feild, C.J.; Cross, A.S.; Hasday, J.D.; Whiteford, C.C.; Nussbaumer, W.A.; Towns, M.; Scalea, T.M. Differential expression of toll-like receptor genes: sepsis compared with sterile inflammation 1 day before sepsis diagnosis. Shock, 2009, 31(3), 238-244.
[40]
Wu, J.F.; Ma, J.; Chen, J.; Ou-Yang, B.; Chen, M.Y.; Li, L.F.; Liu, Y.J.; Lin, A.H.; Guan, X.D. Changes of monocyte human leukocyte antigen-DR expression as a reliable predictor of mortality in severe sepsis. Crit. Care, 2011, 15(5), R220.
[41]
Ryan, T.; Coakley, J.D.; Martin-Loeches, I. Defects in innate and adaptive immunity in patients with sepsis and health care associated infection. Ann. Transl. Med., 2017, 5(22), 447.
[42]
Zhang, Y.; Li, J.; Lou, J.; Zhou, Y.; Bo, L.; Zhu, J.; Zhu, K.; Wan, X.; Cai, Z.; Deng, X. Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients. Crit. Care, 2011, 15(1), R70.
[43]
Shubin, N.J.; Chung, C.S.; Heffernan, D.S.; Irwin, L.R.; Monaghan, S.F.; Ayala, A. BTLA expression contributes to septic morbidity and mortality by inducing innate inflammatory cell dysfunction. J. Leukoc. Biol., 2012, 92(3), 593-603.
[44]
Grimaldi, D.; Louis, S.; Pène, F.; Sirgo, G.; Rousseau, C.; Claessens, Y.E.; Vimeux, L.; Cariou, A.; Mira, J.P.; Hosmalin, A.; Chiche, J.D. Profound and persistent decrease of circulating dendritic cells is associated with ICU-acquired infection in patients with septic shock. Intensive Care Med., 2011, 37(9), 1438-1446.
[45]
Inatsu, A.; Kogiso, M.; Jeschke, M.G.; Asai, A.; Kobayashi, M.; Herndon, D.N.; Suzuki, F. Lack of Th17 cell generation in patients with severe burn injuries. J. Immunol., 2011, 187(5), 2155-2161.
[46]
Venet, F.; Chung, C.S.; Monneret, G.; Huang, X.; Horner, B.; Garber, M.; Ayala, A. Regulatory T cell populations in sepsis and trauma. J. Leukoc. Biol., 2008, 83(3), 523-535.
[47]
Boomer, J.S.; To, K.; Chang, K.C.; Takasu, O.; Osborne, D.F.; Walton, A.H.; Bricker, T.L.; Jarman, S.D., II; Kreisel, D.; Krupnick, A.S.; Srivastava, A.; Swanson, P.E.; Green, J.M.; Hotchkiss, R.S. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA, 2011, 306(23), 2594-2605.
[48]
Lawrence, K.L.; White, P.H.; Morris, G.P.; Jennemann, J.; Phelan, D.L.; Hotchkiss, R.S.; Kollef, M.H. CD4+ lymphocyte adenosine triphosphate determination in sepsis: a cohort study. Crit. Care, 2010, 14(3), R110.
[49]
Venet, F.; Filipe-Santos, O.; Lepape, A.; Malcus, C.; Poitevin-Later, F.; Grives, A.; Plantier, N.; Pasqual, N.; Monneret, G. Decreased T-cell repertoire diversity in sepsis: a preliminary study. Crit. Care Med., 2013, 41(1), 111-119.
[50]
Navarini, A.A.; Lang, K.S.; Verschoor, A.; Recher, M.; Zinkernagel, A.S.; Nizet, V.; Odermatt, B.; Hengartner, H.; Zinkernagel, R.M. Innate immune-induced depletion of bone marrow neutrophils aggravates systemic bacterial infections. Proc. Natl. Acad. Sci. USA, 2009, 106(17), 7107-7112.
[51]
Seok, Y.; Choi, J.R.; Kim, J.; Kim, Y.K.; Lee, J.; Song, J.; Kim, S.J.; Lee, K.A. Delta neutrophil index: a promising diagnostic and prognostic marker for sepsis. Shock, 2012, 37(3), 242-246.
[52]
Alves-Filho, J.C.; Sônego, F.; Souto, F.O.; Freitas, A.; Verri, W.A., Jr; Auxiliadora-Martins, M.; Basile-Filho, A.; McKenzie, A.N.; Xu, D.; Cunha, F.Q.; Liew, F.Y. Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat. Med., 2010, 16(6), 708-712.
[53]
Hotchkiss, R.S.; Nicholson, D.W. Apoptosis and caspases regulate death and inflammation in sepsis. Nat. Rev. Immunol., 2006, 6(11), 813-822.
[54]
Hotchkiss, R.S.; Chang, K.C.; Grayson, M.H.; Tinsley, K.W.; Dunne, B.S.; Davis, C.G.; Osborne, D.F.; Karl, I.E. Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis. Proc. Natl. Acad. Sci. USA, 2003, 100(11), 6724-6729.
[55]
Lin, C.W.; Lo, S.; Hsu, C.; Hsieh, C.H.; Chang, Y.F.; Hou, B.S.; Kao, Y.H.; Lin, C.C.; Yu, M.L.; Yuan, S.S.; Hsieh, Y.C. T-cell autophagy deficiency increases mortality and suppresses immune responses after sepsis. PLoS One, 2014, 9(7), e102066.
[56]
Oami, T.; Watanabe, E.; Hatano, M.; Sunahara, S.; Fujimura, L.; Sakamoto, A.; Ito, C.; Toshimori, K.; Oda, S. Suppression of T cell autophagy results in decreased viability and function of T cells through accelerated apoptosis in a murine sepsis Model. Crit. Care Med., 2017, 45(1), e77-e85.
[57]
Hoogendijk, A.J.; Garcia-Laorden, M.I.; van Vught, L.A.; Wiewel, M.A.; Belkasim-Bohoudi, H.; Duitman, J.; Horn, J.; Schultz, M.J.; Scicluna, B.P.; van ’t Veer, C.; de Vos, A.F.; van der Poll, T. Sepsis patients display a reduced capacity to activate nuclear Factor-κB in multiple cell types. Crit. Care Med., 2017, 45(5), e524-e531.
[58]
Seeley, J.J.; Ghosh, S. Molecular mechanisms of innate memory and tolerance to LPS. J. Leukoc. Biol., 2017, 101(1), 107-119.
[59]
Bikker, R.; Christmann, M.; Preuß, K.; Welz, B.; Friesenhagen, J.; Dittrich-Breiholz, O.; Huber, R.; Brand, K. TNF phase III signalling in tolerant cells is tightly controlled by A20 and CYLD. Cell. Signal., 2017, 37, 123-135.
[60]
Vandereyken, M.M.; Singh, P.; Wathieu, C.P.; Jacques, S.; Zurashvilli, T.; Dejager, L.; Amand, M.; Musumeci, L.; Singh, M.; Moutschen, M.P.; Libert, C.R.F.; Rahmouni, S. Dual-specificity phosphatase 3 deletion protects female, but not male, mice from endotoxemia-induced and polymicrobial-induced septic shock. J. Immunol., 2017, 199(7), 2515-2527.
[61]
Inoue, M.; Shinohara, M.L. Cutting edge: Role of osteopontin and integrin αv in T cell-mediated anti-inflammatory responses in endotoxemia. J. Immunol., 2015, 194(12), 5595-5598.
[62]
Yan, W.; Ding, A.; Kim, H.J.; Zheng, H.; Wei, F.; Ma, X. Progranulin Controls Sepsis via C/EBPα-Regulated Il10 Transcription and Ubiquitin Ligase/Proteasome-Mediated Protein Degradation. J. Immunol., 2016, 197(8), 3393-3405.
[63]
Song, Z.; Zhang, X.; Zhang, L.; Xu, F.; Tao, X.; Zhang, H.; Lin, X.; Kang, L.; Xiang, Y.; Lai, X.; Zhang, Q.; Huang, K.; Dai, Y.; Yin, Y.; Cao, J. Progranulin Plays a Central Role in Host Defense during Sepsis by Promoting Macrophage Recruitment. Am. J. Respir. Crit. Care Med., 2016, 194(10), 1219-1232.
[64]
Hotchkiss, R.S.; Moldawer, L.L.; Opal, S.M.; Reinhart, K.; Turnbull, I.R.; Vincent, J.L. Sepsis and septic shock. Nat. Rev. Dis. Primers, 2016, 2, 16045.
[65]
Venkata, C.; Kashyap, R.; Farmer, J.C.; Afessa, B. Thrombocytopenia in adult patients with sepsis: Incidence, risk factors, and its association with clinical outcome. J. Intensive Care, 2013, 1(1), 9.
[66]
Vieira-de-Abreu, A.; Campbell, R.A.; Weyrich, A.S.; Zimmerman, G.A. Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum. Semin. Immunopathol., 2012, 34(1), 5-30.
[67]
Dewitte, A.; Tanga, A.; Villeneuve, J.; Lepreux, S.; Ouattara, A.; Desmoulière, A.; Combe, C.; Ripoche, J. New frontiers for platelet CD154. Exp. Hematol. Oncol., 2015, 4, 6.
[68]
Thomas, M.R.; Storey, R.F. The role of platelets in inflammation. Thromb. Haemost., 2015, 114(3), 449-458.
[69]
Kapur, R.; Zufferey, A.; Boilard, E.; Semple, J.W. Nouvelle cuisine: Platelets served with inflammation. J. Immunol., 2015, 194(12), 5579-5587.
[70]
Manne, B.K.; Xiang, S.C.; Rondina, M.T. Platelet secretion in inflammatory and infectious diseases. Platelets, 2017, 28(2), 155-164.
[71]
Chen, J.; López, J.A. Interactions of platelets with subendothelium and endothelium. Microcirculation, 2005, 12(3), 235-246.
[72]
Schmidt, E.P.; Kuebler, W.M.; Lee, W.L.; Downey, G.P. Adhesion Molecules: Master Controllers of the Circulatory System. Compr. Physiol., 2016, 6(2), 945-973.
[73]
Sreeramkumar, V.; Adrover, J.M.; Ballesteros, I.; Cuartero, M.I.; Rossaint, J.; Bilbao, I.; Nácher, M.; Pitaval, C.; Radovanovic, I.; Fukui, Y.; McEver, R.P.; Filippi, M.D.; Lizasoain, I.; Ruiz-Cabello, J.; Zarbock, A.; Moro, M.A.; Hidalgo, A. Neutrophils scan for activated platelets to initiate inflammation. Science, 2014, 346(6214), 1234-1238.
[74]
Zuchtriegel, G.; Uhl, B.; Puhr-Westerheide, D.; Pörnbacher, M.; Lauber, K.; Krombach, F.; Reichel, C.A. Platelets Guide Leukocytes to Their Sites of Extravasation. PLoS Biol., 2016, 14(5), e1002459.
[75]
Haselmayer, P.; Grosse-Hovest, L.; von Landenberg, P.; Schild, H.; Radsak, M.P. TREM-1 ligand expression on platelets enhances neutrophil activation. Blood, 2007, 110(3), 1029-1035.
[76]
Stohlawetz, P.; Folman, C.C.; von dem Borne, A.E.; Pernerstorfer, T.; Eichler, H.G.; Panzer, S.; Jilma, B. Effects of endotoxemia on thrombopoiesis in men. Thromb. Haemost., 1999, 81(4), 613-617.
[77]
Michelson, A.D.; Barnard, M.R.; Krueger, L.A.; Valeri, C.R.; Furman, M.I. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: studies in baboons, human coronary intervention, and human acute myocardial infarction. Circulation, 2001, 104(13), 1533-1537.
[78]
Middleton, E.A.; Weyrich, A.S.; Zimmerman, G.A. Platelets in Pulmonary Immune Responses and Inflammatory Lung Diseases. Physiol. Rev., 2016, 96(4), 1211-1259.
[79]
Wan, L.; Bagshaw, S.M.; Langenberg, C.; Saotome, T.; May, C.; Bellomo, R. Pathophysiology of septic acute kidney injury: what do we really know? Crit. Care Med., 2008, 36(Suppl. 4), S198-S203.
[80]
Lerolle, N.; Nochy, D.; Guérot, E.; Bruneval, P.; Fagon, J.Y.; Diehl, J.L.; Hill, G. Histopathology of septic shock induced acute kidney injury: apoptosis and leukocytic infiltration. Intensive Care Med., 2010, 36(3), 471-478.
[81]
Mastorakos, G.; Chrousos, G.P.; Weber, J.S. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J. Clin. Endocrinol. Metab., 1993, 77(6), 1690-1694.
[82]
Boonen, E.; Vervenne, H.; Meersseman, P.; Andrew, R.; Mortier, L.; Declercq, P.E.; Vanwijngaerden, Y.M.; Spriet, I.; Wouters, P.J.; Vander Perre, S.; Langouche, L.; Vanhorebeek, I.; Walker, B.R.; Van den Berghe, G. Reduced cortisol metabolism during critical illness. N. Engl. J. Med., 2013, 368(16), 1477-1488.
[83]
Arafah, B.M. Hypothalamic pituitary adrenal function during critical illness: limitations of current assessment methods. J. Clin. Endocrinol. Metab., 2006, 91(10), 3725-3745.
[84]
Beishuizen, A.; Thijs, L.G.; Vermes, I. Patterns of corticosteroid-binding globulin and the free cortisol index during septic shock and multitrauma. Intensive Care Med., 2001, 27(10), 1584-1591.
[85]
Quatrini, L.; Wieduwild, E.; Guia, S.; Bernat, C.; Glaichenhaus, N.; Vivier, E.; Ugolini, S. Host resistance to endotoxic shock requires the neuroendocrine regulation of group 1 innate lymphoid cells. J. Exp. Med., 2017, 214(12), 3531-3541.
[86]
Molijn, G.J.; Spek, J.J.; van Uffelen, J.C.; de Jong, F.H.; Brinkmann, A.O.; Bruining, H.A.; Lamberts, S.W.; Koper, J.W. Differential adaptation of glucocorticoid sensitivity of peripheral blood mononuclear leukocytes in patients with sepsis or septic shock. J. Clin. Endocrinol. Metab., 1995, 80(6), 1799-1803.
[87]
Ingels, C.; Gunst, J.; Van den Berghe, G. Endocrine and Metabolic Alterations in Sepsis and Implications for Treatment. Crit. Care Clin., 2018, 34(1), 81-96.
[88]
Annane, D.; Sébille, V.; Troché, G.; Raphaël, J.C.; Gajdos, P.; Bellissant, E. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA, 2000, 283(8), 1038-1045.
[89]
Endoh, M. Cardiac Ca2+ signaling and Ca2+ sensitizers. Circ. J., 2008, 72(12), 1915-1925.
[90]
Parissis, J.T.; Farmakis, D.; Kremastinos, D.T. Anti-inflammatory effects of levosimendan in decompensated heart failure: impact on weight loss and anemia. Am. J. Cardiol., 2005, 95(7), 923-924.
[91]
Vieillard-Baron, A.; Caille, V.; Charron, C.; Belliard, G.; Page, B.; Jardin, F. Actual incidence of global left ventricular hypokinesia in adult septic shock. Crit. Care Med., 2008, 36(6), 1701-1706.
[92]
Tsao, C.M.; Li, K.Y.; Chen, S.J.; Ka, S.M.; Liaw, W.J.; Huang, H.C.; Wu, C.C. Levosimendan attenuates multiple organ injury and improves survival in peritonitis-induced septic shock: studies in a rat model. Crit. Care, 2014, 18(6), 652.
[93]
Wang, Q.; Yokoo, H.; Takashina, M.; Sakata, K.; Ohashi, W.; Abedelzaher, L.A.; Imaizumi, T.; Sakamoto, T.; Hattori, K.; Matsuda, N.; Hattori, Y. Anti-Inflammatory Profile of Levosimendan in Cecal Ligation-Induced Septic Mice and in Lipopolysaccharide-Stimulated Macrophages. Crit. Care Med., 2015, 43(11), e508-e520.
[94]
Zager, R.A.; Johnson, A.C.; Lund, S.; Hanson, S.Y.; Abrass, C.K. Levosimendan protects against experimental endotoxemic acute renal failure. Am. J. Physiol. Renal Physiol., 2006, 290(6), F1453-F1462.
[95]
Matejovic, M.; Krouzecky, A.; Radej, J.; Novak, I. Successful reversal of resistent hypodynamic septic shock with levosimendan. Acta Anaesthesiol. Scand., 2005, 49(1), 127-128.
[96]
Morelli, A.; De Castro, S.; Teboul, J.L.; Singer, M.; Rocco, M.; Conti, G.; De Luca, L.; Di Angelantonio, E.; Orecchioni, A.; Pandian, N.G.; Pietropaoli, P. Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression. Intensive Care Med., 2005, 31(5), 638-644.
[97]
Sareila, O.; Korhonen, R.; Auvinen, H.; Hämäläinen, M.; Kankaanranta, H.; Nissinen, E.; Moilanen, E. Effects of levo- and dextrosimendan on NF-kappaB-mediated transcription, iNOS expression and NO production in response to inflammatory stimuli. Br. J. Pharmacol., 2008, 155(6), 884-895.
[98]
Gordon, A.C.; Perkins, G.D.; Singer, M.; McAuley, D.F.; Orme, R.M.; Santhakumaran, S.; Mason, A.J.; Cross, M.; Al-Beidh, F.; Best-Lane, J.; Brealey, D.; Nutt, C.L.; McNamee, J.J.; Reschreiter, H.; Breen, A.; Liu, K.D.; Ashby, D. Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis. N. Engl. J. Med., 2016, 375(17), 1638-1648.
[99]
Fink, M.P. Ethyl pyruvate: a novel anti-inflammatory agent. J. Intern. Med., 2007, 261(4), 349-362.
[100]
Ulloa, L.; Ochani, M.; Yang, H.; Tanovic, M.; Halperin, D.; Yang, R.; Czura, C.J.; Fink, M.P.; Tracey, K.J. Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc. Natl. Acad. Sci. USA, 2002, 99(19), 12351-12356.
[101]
Miyaji, T.; Hu, X.; Yuen, P.S.; Muramatsu, Y.; Iyer, S.; Hewitt, S.M.; Star, R.A. Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice. Kidney Int., 2003, 64(5), 1620-1631.
[102]
Leelahavanichkul, A.; Yasuda, H.; Doi, K.; Hu, X.; Zhou, H.; Yuen, P.S.; Star, R.A. Methyl-2-acetamidoacrylate, an ethyl pyruvate analog, decreases sepsis-induced acute kidney injury in mice. Am. J. Physiol. Renal Physiol., 2008, 295(6), F1825-F1835.
[103]
Goldstein, J.L.; Brown, M.S. The LDL receptor. Arterioscler. Thromb. Vasc. Biol., 2009, 29(4), 431-438.
[104]
Greenwood, J.; Mason, J.C. Statins and the vascular endothelial inflammatory response. Trends Immunol., 2007, 28(2), 88-98.
[105]
Jacobson, J.R.; Barnard, J.W.; Grigoryev, D.N.; Ma, S.F.; Tuder, R.M.; Garcia, J.G. Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol., 2005, 288(6), L1026-L1032.
[106]
Yao, H.W.; Mao, L.G.; Zhu, J.P. Protective effects of pravastatin in murine lipopolysaccharide-induced acute lung injury. Clin. Exp. Pharmacol. Physiol., 2006, 33(9), 793-797.
[107]
Takano, K.; Yamamoto, S.; Tomita, K.; Takashina, M.; Yokoo, H.; Matsuda, N.; Takano, Y.; Hattori, Y. Successful treatment of acute lung injury with pitavastatin in septic mice: potential role of glucocorticoid receptor expression in alveolar macrophages. J. Pharmacol. Exp. Ther., 2011, 336(2), 381-390.
[108]
Rinaldi, B.; Donniacuo, M.; Esposito, E.; Capuano, A.; Sodano, L.; Mazzon, E.; Di Palma, D.; Paterniti, I.; Cuzzocrea, S.; Rossi, F. PPARα mediates the anti-inflammatory effect of simvastatin in an experimental model of zymosan-induced multiple organ failure. Br. J. Pharmacol., 2011, 163(3), 609-623.
[109]
Gupta, R.; Plantinga, L.C.; Fink, N.E.; Melamed, M.L.; Coresh, J.; Fox, C.S.; Levin, N.W.; Powe, N.R. Statin use and sepsis events [corrected] in patients with chronic kidney disease. JAMA, 2007, 297(13), 1455-1464.
[110]
Schurr, J.W.; Wu, W.; Smith-Hannah, A.; Smith, C.J.; Barrera, R. Incidence of sepsis and mortality with prior exposure of HMG-COA reductase inhibitors in a surgical intensive care population. Shock, 2016, 45(1), 10-15.
[111]
Lugnier, C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol. Ther., 2006, 109(3), 366-398.
[112]
Netherton, S.J.; Maurice, D.H. Vascular endothelial cell cyclic nucleotide phosphodiesterases and regulated cell migration: Implications in angiogenesis. Mol. Pharmacol., 2005, 67(1), 263-272.
[113]
Buenestado, A.; Grassin-Delyle, S.; Guitard, F.; Naline, E.; Faisy, C.; Israël-Biet, D.; Sage, E.; Bellamy, J.F.; Tenor, H.; Devillier, P. Roflumilast inhibits the release of chemokines and TNF-α from human lung macrophages stimulated with lipopolysaccharide. Br. J. Pharmacol., 2012, 165(6), 1877-1890.
[114]
Flemming, S.; Schlegel, N.; Wunder, C.; Meir, M.; Baar, W.; Wollborn, J.; Roewer, N.; Germer, C.T.; Schick, M.A. Phosphodiesterase 4 inhibition dose dependently stabilizes microvascular barrier functions and microcirculation in a rodent model of polymicrobial sepsis. Shock, 2014, 41(6), 537-545.
[115]
Oishi, H.; Takano, K.; Tomita, K.; Takebe, M.; Yokoo, H.; Yamazaki, M.; Hattori, Y. Olprinone and colforsin daropate alleviate septic lung inflammation and apoptosis through CREB-independent activation of the Akt pathway. Am. J. Physiol. Lung Cell. Mol. Physiol., 2012, 303(2), L130-L140.
[116]
Mizushige, K.; Ueda, T.; Yukiiri, K.; Suzuki, H. Olprinone: a phosphodiesterase III inhibitor with positive inotropic and vasodilator effects. Cardiovasc. Drug Rev., 2002, 20(3), 163-174.
[117]
Sun, C.X.; Young, H.W.; Molina, J.G.; Volmer, J.B.; Schnermann, J.; Blackburn, M.R. A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury. J. Clin. Invest., 2005, 115(1), 35-43.
[118]
Csóka, B.; Németh, Z.H.; Rosenberger, P.; Eltzschig, H.K.; Spolarics, Z.; Pacher, P.; Selmeczy, Z.; Koscsó, B.; Himer, L.; Vizi, E.S.; Blackburn, M.R.; Deitch, E.A.; Haskó, G. A2B adenosine receptors protect against sepsis-induced mortality by dampening excessive inflammation. J. Immunol., 2010, 185(1), 542-550.
[119]
Wilson, C.N.; Vance, C.O.; Lechner, M.G.; Matuschak, G.M.; Lechner, A.J. Adenosine A1 receptor antagonist, L-97-1, improves survival and protects the kidney in a rat model of cecal ligation and puncture induced sepsis. Eur. J. Pharmacol., 2014, 740, 346-352.
[120]
Neely, C.F.; Jin, J.; Keith, I.M. A1-adenosine receptor antagonists block endotoxin-induced lung injury. Am. J. Physiol., 1997, 272(2 Pt 1), L353-L361.
[121]
Schingnitz, U.; Hartmann, K.; Macmanus, C.F.; Eckle, T.; Zug, S.; Colgan, S.P.; Eltzschig, H.K. Signaling through the A2B adenosine receptor dampens endotoxin-induced acute lung injury. J. Immunol., 2010, 184(9), 5271-5279.
[122]
Folkesson, H.G.; Kuzenko, S.R.; Lipson, D.A.; Matthay, M.A.; Simmons, M.A. The adenosine 2A receptor agonist GW328267C improves lung function after acute lung injury in rats. Am. J. Physiol. Lung Cell. Mol. Physiol., 2012, 303(3), L259-L271.
[123]
Jacobson, K.A. Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol. Sci., 1998, 19(5), 184-191.
[124]
Lee, H.S.; Chung, H.J.; Lee, H.W.; Jeong, L.S.; Lee, S.K. Suppression of inflammation response by a novel A3 adenosine receptor agonist thio-Cl-IB-MECA through inhibition of Akt and NF-κB signaling. Immunobiology, 2011, 216(9), 997-1003.
[125]
Haskó, G.; Németh, Z.H.; Vizi, E.S.; Salzman, A.L.; Szabó, C. An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-gamma production and prevents lethality in endotoxemic mice. Eur. J. Pharmacol., 1998, 358(3), 261-268.
[126]
Khoa, N.D.; Montesinos, M.C.; Reiss, A.B.; Delano, D.; Awadallah, N.; Cronstein, B.N. Inflammatory cytokines regulate function and expression of adenosine A(2A) receptors in human monocytic THP-1 cells. J. Immunol., 2001, 167(7), 4026-4032.
[127]
Ma, C.Y.; Chang, W.E.; Shi, G.Y.; Chang, B.Y.; Cheng, S.E.; Shih, Y.T.; Wu, H.L. Recombinant thrombomodulin inhibits lipopolysaccharide-induced inflammatory response by blocking the functions of CD14. J. Immunol., 2015, 194(4), 1905-1915.
[128]
Chen, C.W.; Mittal, R.; Klingensmith, N.J.; Burd, E.M.; Terhorst, C.; Martin, G.S.; Coopersmith, C.M.; Ford, M.L. Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in Experimental Sepsis. J. Immunol., 2017, 199(6), 1961-1966.
[129]
Toya, S.P.; Li, F.; Bonini, M.G.; Gomez, I.; Mao, M.; Bachmaier, K.W.; Malik, A.B. Interaction of a specific population of human embryonic stem cell-derived progenitor cells with CD11b+ cells ameliorates sepsis-induced lung inflammatory injury. Am. J. Pathol., 2011, 178(1), 313-324.
[130]
Luo, C.J.; Zhang, F.J.; Zhang, L.; Geng, Y.Q.; Li, Q.G.; Hong, Q.; Fu, B.; Zhu, F.; Cui, S.Y.; Feng, Z.; Sun, X.F.; Chen, X.M. Mesenchymal stem cells ameliorate sepsis-associated acute kidney injury in mice. Shock, 2014, 41(2), 123-129.
[131]
Krasnodembskaya, A.; Samarani, G.; Song, Y.; Zhuo, H.; Su, X.; Lee, J.W.; Gupta, N.; Petrini, M.; Matthay, M.A. Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am. J. Physiol. Lung Cell. Mol. Physiol., 2012, 302(10), L1003-L1013.
[132]
Guillamat-Prats, R.; Camprubí-Rimblas, M.; Bringué, J.; Tantinyà, N.; Artigas, A. Cell therapy for the treatment of sepsis and acute respiratory distress syndrome. Ann. Transl. Med., 2017, 5(22), 446.
[133]
Németh, K.; Leelahavanichkul, A.; Yuen, P.S.; Mayer, B.; Parmelee, A.; Doi, K.; Robey, P.G.; Leelahavanichkul, K.; Koller, B.H.; Brown, J.M.; Hu, X.; Jelinek, I.; Star, R.A.; Mezey, E. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat. Med., 2009, 15(1), 42-49.
[134]
Güldner, A.; Maron-Gutierrez, T.; Abreu, S.C.; Xisto, D.G.; Senegaglia, A.C.; Barcelos, P.R.; Silva, J.D.; Brofman, P.; de Abreu, M.G.; Rocco, P.R. Expanded endothelial progenitor cells mitigate lung injury in septic mice. Stem Cell Res. Ther., 2015, 6, 230.
[135]
Xu, X.; Yang, J.; Li, N.; Wu, R.; Tian, H.; Song, H.; Wang, H. Role of endothelial progenitor cell transplantation in rats with sepsis. Transplant. Proc., 2015, 47(10), 2991-3001.
[136]
Fan, H.; Goodwin, A.J.; Chang, E.; Zingarelli, B.; Borg, K.; Guan, S.; Halushka, P.V.; Cook, J.A. Endothelial progenitor cells and a stromal cell-derived factor-1α analogue synergistically improve survival in sepsis. Am. J. Respir. Crit. Care Med., 2014, 189(12), 1509-1519.
[137]
Aziz, M.; Holodick, N.E.; Rothstein, T.L.; Wang, P. B-1a Cells Protect Mice from Sepsis: Critical Role of CREB. J. Immunol., 2017, 199, 750-760.
[138]
Jin, L.; Batra, S.; Jeyaseelan, S. Deletion of Nlrp3 Augments Survival during Polymicrobial Sepsis by Decreasing Autophagy and Enhancing Phagocytosis. J. Immunol., 2017, 198(3), 1253-1262.
[139]
Parratt, J.R. Nitric oxide in sepsis and endotoxaemia. J. Antimicrob. Chemother., 1998, 41(Suppl. A), 31-39.
[140]
Parihar, A.; Parihar, M.S.; Milner, S.; Bhat, S. Oxidative stress and anti-oxidative mobilization in burn injury. Burns, 2008, 34(1), 6-17.
[141]
Annane, D.; Sébille, V.; Charpentier, C.; Bollaert, P.E.; François, B.; Korach, J.M.; Capellier, G.; Cohen, Y.; Azoulay, E.; Troché, G.; Chaumet-Riffaud, P.; Bellissant, E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA, 2002, 288(7), 862-871.
[142]
Sjakste, N.; Baumane, L.; Boucher, J.L.; Dzintare, M.; Meirena, D.; Sjakste, J.; Lauberte, L.; Kalvinsh, I. Effects of gamma-butyrobetaine and mildronate on nitric oxide production in lipopolysaccharide-treated rats. Basic Clin. Pharmacol. Toxicol., 2004, 94(1), 46-50.
[143]
Kim, J.Y.; Lee, S.M. Effect of ascorbic acid on hepatic vasoregulatory gene expression during polymicrobial sepsis. Life Sci., 2004, 75(16), 2015-2026.
[144]
Kim, J.Y.; Lee, S.M. Vitamins C and E protect hepatic cytochrome P450 dysfunction induced by polymicrobial sepsis. Eur. J. Pharmacol., 2006, 534(1-3), 202-209.
[145]
Sener, G.; Toklu, H.; Ercan, F.; Erkanli, G. Protective effect of beta-glucan against oxidative organ injury in a rat model of sepsis. Int. Immunopharmacol., 2005, 5(9), 1387-1396.
[146]
Magrone, T.; Kumazawa, Y.; Jirillo, E. Polyphenol-mediated beneficial effects in healthy status and disease with special references to immune-based mechanisms. In: Polyphenols in Human Health and Disease; Watson, R.R.; Preedy, V.; Zibaldi, S., Eds.; Elsevier, 2014, Vol 7, pp. 467-479.
[147]
Pallarès, V.; Fernández-Iglesias, A.; Cedó, L.; Castell-Auví, A.; Pinent, M.; Ardévol, A.; Salvadó, M.J.; Garcia-Vallvé, S.; Blay, M. Grape seed procyanidin extract reduces the endotoxic effects induced by lipopolysaccharide in rats. Free Radic. Biol. Med., 2013, 60, 107-114.
[148]
Li, C.Y.; Suzuki, K.; Hung, Y.L.; Yang, M.S.; Yu, C.P.; Lin, S.P.; Hou, Y.C.; Fang, S.H. Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation. Am. J. Chin. Med., 2017, 45(4), 847-861.
[149]
Magrone, T.; Panaro, M.A.; Jirillo, E.; Covelli, V. Molecular effects elicited in vitro by red wine on human healthy peripheral blood mononuclear cells: potential therapeutical application of polyphenols to diet-related chronic diseases. Curr. Pharm. Des., 2008, 14(26), 2758-2766.
[150]
Kumazoe, M.; Yamashita, M.; Nakamura, Y.; Takamatsu, K.; Bae, J.; Yamashita, S.; Yamada, S.; Onda, H.; Nojiri, T.; Kangawa, K.; Tachibana, H. Green Tea Polyphenol EGCG Upregulates Tollip Expression by Suppressing Elf-1 Expression. J. Immunol., 2017, 199(9), 3261-3269.
[151]
Clemente-Postigo, M.; Queipo-Ortuño, M.I.; Boto-Ordoñez, M.; Coin-Aragüez, L.; Roca-Rodriguez, M.M.; Delgado-Lista, J.; Cardona, F.; Andres-Lacueva, C.; Tinahones, F.J. Effect of acute and chronic red wine consumption on lipopolysaccharide concentrations. Am. J. Clin. Nutr., 2013, 97(5), 1053-1061.
[152]
Matsumoto, S.; Koga, H.; Kusaka, J. Effects of the antioxidant-enriched concentrated liquid diet ANOM on oxidative stress and multiple organ injury in patients with septic shock: a pilot study. J. Anesth. Clin. Res., 2011, 2, 1-5.
[153]
Manzanares, W.; Biestro, A.; Galusso, F.; Torre, M.H.; Mañay, N.; Pittini, G.; Facchin, G.; Hardy, G. Serum selenium and glutathione peroxidase-3 activity: biomarkers of systemic inflammation in the critically ill? Intensive Care Med., 2009, 35(5), 882-889.
[154]
Prabhu, K.S.; Zamamiri-Davis, F.; Stewart, J.B.; Thompson, J.T.; Sordillo, L.M.; Reddy, C.C. Selenium deficiency increases the expression of inducible nitric oxide synthase in RAW 264.7 macrophages: role of nuclear factor-kappaB in up-regulation. Biochem. J., 2002, 366(Pt. 1), 203-209.
[155]
Angstwurm, M.W.; Engelmann, L.; Zimmermann, T.; Lehmann, C.; Spes, C.H.; Abel, P.; Strauss, R.; Meier-Hellmann, A.; Insel, R.; Radke, J.; Schüttler, J.; Gärtner, R. Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit. Care Med., 2007, 35(1), 118-126.
[156]
Manzanares, W.; Dhaliwal, R.; Jiang, X.; Murch, L.; Heyland, D.K. Antioxidant micronutrients in the critically ill: A systematic review and meta-analysis. Crit. Care, 2012, 16(2), R66.
[157]
Hardy, G.; Hardy, I.; Manzanares, W. Selenium supplementation in the critically ill. Nutr. Clin. Pract., 2012, 27(1), 21-33.
[158]
Angstwurm, M.W.; Schottdorf, J.; Schopohl, J.; Gaertner, R. Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome. Crit. Care Med., 1999, 27(9), 1807-1813.
[159]
Gammoh, N.Z.; Rink, L. Zinc in Infection and Inflammation. Nutrients, 2017, 9(6), E624.
[160]
Mertens, K.; Lowes, D.A.; Webster, N.R.; Talib, J.; Hall, L.; Davies, M.J.; Beattie, J.H.; Galley, H.F. Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation. Br. J. Anaesth., 2015, 114(6), 990-999.
[161]
Wong, H.R.; Shanley, T.P.; Sakthivel, B.; Cvijanovich, N.; Lin, R.; Allen, G.L.; Thomas, N.J.; Doctor, A.; Kalyanaraman, M.; Tofil, N.M.; Penfil, S.; Monaco, M.; Tagavilla, M.A.; Odoms, K.; Dunsmore, K.; Barnes, M.; Aronow, B.J. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol. Genomics, 2007, 30(2), 146-155.
[162]
Nowak, J.E.; Harmon, K.; Caldwell, C.C.; Wong, H.R. Prophylactic zinc supplementation reduces bacterial load and improves survival in a murine model of sepsis. Pediatr. Crit. Care Med., 2012, 13(5), e323-e329.
[163]
Knoell, D.L.; Julian, M.W.; Bao, S.; Besecker, B.; Macre, J.E.; Leikauf, G.D.; DiSilvestro, R.A.; Crouser, E.D. Zinc deficiency increases organ damage and mortality in a murine model of polymicrobial sepsis. Crit. Care Med., 2009, 37(4), 1380-1388.
[164]
Ganatra, H.A.; Varisco, B.M.; Harmon, K.; Lahni, P.; Opoka, A.; Wong, H.R. Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis. Innate Immun., 2017, 23(1), 67-76.
[165]
Solan, P.D.; Dunsmore, K.E.; Denenberg, A.G.; Odoms, K.; Zingarelli, B.; Wong, H.R. A novel role for matrix metalloproteinase-8 in sepsis. Crit. Care Med., 2012, 40(2), 379-387.
[166]
Cvijanovich, N.Z.; King, J.C.; Flori, H.R.; Gildengorin, G.; Vinks, A.A.; Wong, H.R. Safety and Dose Escalation Study of Intravenous Zinc Supplementation in Pediatric Critical Illness. JPEN J. Parenter. Enteral Nutr., 2016, 40(6), 860-868.
[167]
Caccavo, D.; Afeltra, A.; Pece, S.; Giuliani, G.; Freudenberg, M.; Galanos, C.; Jirillo, E. Lactoferrin-lipid A-lipopolysaccharide interaction: inhibition by anti-human lactoferrin monoclonal antibody AGM 10.14. Infect. Immun., 1999, 67(9), 4668-4672.
[168]
Caccavo, D.; Pellegrino, N.M.; Altamura, M.; Rigon, A.; Amati, L.; Amoroso, A.; Jirillo, E. Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application. J. Endotoxin Res., 2002, 8(6), 403-417.
[169]
Decembrino, L.; DeAmici, M.; De Silvestri, A.; Manzoni, P.; Paolillo, P.; Stronati, M. Plasma lactoferrin levels in newborn preterm infants with sepsis. J. Matern. Fetal Neonatal Med., 2017, 30(23), 2890-2893.
[170]
Pammi, M.; Suresh, G. Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst. Rev., 2017, 6, CD007137.
[171]
Sharma, D.; Shastri, S.; Sharma, P. Role of lactoferrin in neonatal care: A systematic review. J. Matern. Fetal Neonatal Med., 2017, 30(16), 1920-1932.
[172]
Meyer, M.P.; Alexander, T. Reduction in necrotizing enterocolitis and improved outcomes in preterm infants following routine supplementation with Lactobacillus GG in combination with bovine lactoferrin. J. Neonatal Perinatal Med., 2017, 10(3), 249-255.
[173]
He, Y.; Lawlor, N.T.; Newburg, D.S. Human Milk Components Modulate Toll-Like Receptor-Mediated Inflammation. Adv. Nutr., 2016, 7(1), 102-111.
[174]
Shimizu, K.; Ogura, H.; Hamasaki, T.; Goto, M.; Tasaki, O.; Asahara, T.; Nomoto, K.; Morotomi, M.; Matsushima, A.; Kuwagata, Y.; Sugimoto, H. Altered gut flora are associated with septic complications and death in critically ill patients with systemic inflammatory response syndrome. Dig. Dis. Sci., 2011, 56(4), 1171-1177.
[175]
Magrone, T.; Jirillo, E. The interplay between the gut immune system and microbiota in health and disease: nutraceutical intervention for restoring intestinal homeostasis. Curr. Pharm. Des., 2013, 19(7), 1329-1342.
[176]
Kamada, N.; Núñez, G. Regulation of the immune system by the resident intestinal bacteria. Gastroenterology, 2014, 146(6), 1477-1488.
[177]
Cabrera-Perez, J.; Badovinac, V.P.; Griffith, T.S. Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease. Exp. Biol. Med. (Maywood), 2017, 242(2), 127-139.
[178]
Haak, B.W.; Wiersinga, W.J. The role of the gut microbiota in sepsis. Lancet Gastroenterol. Hepatol., 2017, 2(2), 135-143.
[179]
Khoruts, A.; Sadowsky, M.J. Understanding the mechanisms of faecal microbiota transplantation. Nat. Rev. Gastroenterol. Hepatol., 2016, 13(9), 508-516.
[180]
Akrami, K.; Sweeney, D.A. The microbiome of the critically ill patient. Curr. Opin. Crit. Care, 2018, 24(1), 49-54.
[181]
Arumugam, S.; Lau, C.S.M.; Chamberlain, R.S. Probiotics and synbiotics decrease postoperative sepsis in elective gastrointestinal surgical patients: a meta-analysis. J. Gastrointest. Surg., 2016, 20(6), 1123-1131.
[182]
Panigrahi, P.; Parida, S.; Nanda, N.C.; Satpathy, R.; Pradhan, L.; Chandel, D.S.; Baccaglini, L.; Mohapatra, A.; Mohapatra, S.S.; Misra, P.R.; Chaudhry, R.; Chen, H.H.; Johnson, J.A.; Morris, J.G.; Paneth, N.; Gewolb, I.H. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature, 2017, 548(7668), 407-412.
[183]
Oláh, A.; Belágyi, T.; Pótó, L.; Romics, L., Jr; Bengmark, S. Synbiotic control of inflammation and infection in severe acute pancreatitis: a prospective, randomized, double blind study. Hepatogastroenterology, 2007, 54(74), 590-594.

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