Abstract
The hosts inflammatory response to sepsis can be divided into two phases, the initial detection and response to the pathogen initiated by the innate immune response, and the persistent inflammatory state characterized by multiple organ dysfunction syndrome (MODS). New therapies aimed at pathogen recognition receptors (PRRs) particularly the TLRs and the NOD-like receptors offer hope to suppress the initial inflammatory response in early sepsis and to bolster this response in late sepsis. The persistence of MODS after the initial inflammatory surge can also be a determining factor to host survival. MODS is due to the cellular damage and death induced by sepsis. The mechanism of this cell death depends in part upon mitochondrial dysfunction. Damaged mitochondria have increased membrane permeability prompting their autophagic removal if few mitochondria are involved but apoptotic cell death may occur if the mitochondrial losses are more extensive. In addition. severe loss of mitochondria results in low cell energy stores, necrotic cell death, and increased inflammation driven by the release of cell components such as HMGB1. Therapies, which aim at improving cellular energy reserves such as the promotion of mitochondrial biogenesis by insulin, may have a role in future sepsis therapies. Finally, both the inflammatory responses and the susceptibility to organ failure may be modulated by nutritional status and micronutrients, such as zinc, Therapies aimed at micronutrient repletion may further augment approaches targeting PRR function and mitochondrial viability.
Keywords: Sepsis, pathogen, multiple organ dysfunction syndrome (MODS), pathogen recognition receptors (PRRs), mitochondria, necrotic cell death, inflammation, biogenesis
Current Pharmaceutical Design
Title: Sepsis: Links between Pathogen Sensing and Organ Damage
Volume: 14 Issue: 19
Author(s): Elliott Crouser, Matthew Exline, Daren Knoell and Mark D. Wewers
Affiliation:
Keywords: Sepsis, pathogen, multiple organ dysfunction syndrome (MODS), pathogen recognition receptors (PRRs), mitochondria, necrotic cell death, inflammation, biogenesis
Abstract: The hosts inflammatory response to sepsis can be divided into two phases, the initial detection and response to the pathogen initiated by the innate immune response, and the persistent inflammatory state characterized by multiple organ dysfunction syndrome (MODS). New therapies aimed at pathogen recognition receptors (PRRs) particularly the TLRs and the NOD-like receptors offer hope to suppress the initial inflammatory response in early sepsis and to bolster this response in late sepsis. The persistence of MODS after the initial inflammatory surge can also be a determining factor to host survival. MODS is due to the cellular damage and death induced by sepsis. The mechanism of this cell death depends in part upon mitochondrial dysfunction. Damaged mitochondria have increased membrane permeability prompting their autophagic removal if few mitochondria are involved but apoptotic cell death may occur if the mitochondrial losses are more extensive. In addition. severe loss of mitochondria results in low cell energy stores, necrotic cell death, and increased inflammation driven by the release of cell components such as HMGB1. Therapies, which aim at improving cellular energy reserves such as the promotion of mitochondrial biogenesis by insulin, may have a role in future sepsis therapies. Finally, both the inflammatory responses and the susceptibility to organ failure may be modulated by nutritional status and micronutrients, such as zinc, Therapies aimed at micronutrient repletion may further augment approaches targeting PRR function and mitochondrial viability.
Export Options
About this article
Cite this article as:
Crouser Elliott, Exline Matthew, Knoell Daren and Wewers D. Mark, Sepsis: Links between Pathogen Sensing and Organ Damage, Current Pharmaceutical Design 2008; 14 (19) . https://dx.doi.org/10.2174/138161208784980572
DOI https://dx.doi.org/10.2174/138161208784980572 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Gene Therapy to Improve Pancreatic Islet Transplantation for Type 1 Diabetes Mellitus
Current Diabetes Reviews Specific Immune Intervention with Monoclonal Antibodies for the Treatment of Multiple Sclerosis
Current Medicinal Chemistry Regulation of the PI3K-Akt Network: Current Status and a Promise for the Treatment of Human Diseases
Current Signal Transduction Therapy Neurotrophic and Neuroprotective Effects of Muscle Contraction
Current Pharmaceutical Design Potential of Flavonoids as Anti-inflammatory Agents: Modulation of Pro- Inflammatory Gene Expression and Signal Transduction Pathways
Current Drug Metabolism Advantages of Structure-Based Drug Design Approaches in Neurological Disorders
Current Neuropharmacology Using an Ancient Tool for Igniting and Propagating Immune Tolerance: IDO as an Inducer and Amplifier of Regulatory T Cell Functions
Current Medicinal Chemistry Neuroimmune Crosstalk in CNS Disorders: The Histamine Connection
Current Pharmaceutical Design Recent Advances in Pegylated Interferon Antiviral Therapy of Chronic Hepatitis C
Anti-Infective Agents in Medicinal Chemistry Euglycemic Diabetic Ketoacidosis: A Review
Current Diabetes Reviews Bioactive Compounds Effective Against Type 2 Diabetes Mellitus: A Systematic Review
Current Topics in Medicinal Chemistry Polymeric Nanoparticles for Ophthalmic Drug Delivery: An Update on Research and Patenting Activity
Recent Patents on Nanomedicine miRNAs in Insulin Resistance and Diabetes-Associated Pancreatic Cancer: The ‘Minute and Miracle’ Molecule Moving as a Monitor in the ‘Genomic Galaxy’
Current Drug Targets Anti-TNF-α Antibody Therapies in Autoimmune Diseases
Current Topics in Medicinal Chemistry The Extracellular Matrix of Blood Vessels
Current Pharmaceutical Design Involvement of Regulatory T Cells in HIV Immunopathogenesis
Current HIV Research The Axis of Thrombospondin-1, Transforming Growth Factor Beta and Connective Tissue Growth Factor: An Emerging Therapeutic Target in Rheumatoid Arthritis
Current Vascular Pharmacology Emerging Role of Circular RNAs in Kidney Diseases in Nephrology
Current Drug Targets “Self-Antigenic Universe” and Tuberculosis Vaccine Development
Current Pharmacogenomics and Personalized Medicine Targeting Indoleamine 2,3-dioxygenase (IDO) to Counteract Tumour- Induced ImmuneDysfunction: From Biochemistry to Clinical Development
Endocrine, Metabolic & Immune Disorders - Drug Targets