Immunomodulatory Effects of Antipsychotic Drugs in Whole Blood Cell Cultures from Healthy Subjects

Author(s): Eun-Jeong Kim, Yong-Ku Kim*

Journal Name: Current Psychiatry Research and Reviews
Formerly: Current Psychiatry Reviews

Volume 15 , Issue 4 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: We aimed to evaluate the effects of various antipsychotics on the in vitro production of C-reactive protein (CRP) in whole blood cell cultures from healthy volunteers. The evaluation was performed using haloperidol, quetiapine, clozapine, amisulpride, and chlorpromazine.

Methods: Antipsychotic agents were added to the participants' whole blood samples, and the resulting CRP levels were measured. For each agent, three different concentrations were tested: the therapeutic concentration, one-tenth the therapeutic concentration, and ten times the therapeutic concentration. The differences in CRP concentrations before and after drug administration were investigated.

Results: The Friedman test showed that haloperidol, amisulpride, and chlorpromazine significantly increased CRP levels in the blood culture samples; however, clozapine and quetiapine did not increase CRP levels. In the case of chlorpromazine, elevated CRP levels were noted at all concentrations tested.

Conclusion: Our study suggests that some antipsychotics elevate CRP levels in vitro. These results agree with previous studies showing that antipsychotics have immunomodulatory effects. Future research will clarify our findings and our understanding of antipsychotic drugs and their impact on immune regulation.

Keywords: Schizophrenia, antipsychotic agents, inflammation, C-reactive protein, blood cell cultures, immune regulation.

[1]
Snyder SH, Banerjee SP, Yamamura HI, Greenberg D. Drugs, neurotransmitters, and schizophrenia. Science 1974; 184(4143): 1243-53.
[http://dx.doi.org/10.1126/science.184.4143.1243] [PMID: 17784215]
[2]
Lindenmayer J-P. Treatment refractory schizophrenia. Psychiatr Q 2000; 71(4): 373-84.
[http://dx.doi.org/10.1023/A:1004640408501] [PMID: 11025914]
[3]
Rothermundt M, Arolt V, Bayer TA. Review of immunological and immunopathological findings in schizophrenia. Brain Behav Immun 2001; 15(4): 319-39.
[http://dx.doi.org/10.1006/brbi.2001.0648] [PMID: 11782102]
[4]
Raison CL, Miller AH, Eds. The neuroimmunology of stress and depression Seminars in clinical neuropsychiatry. Philadelphia: WB Saunders Company 2001.
[5]
Remlinger-Molenda A, Rybakowski J. Neuroimmunology of bipolar affective disorder. Psychiatr Pol 2010; 44(1): 27-38.
[PMID: 20449978]
[6]
Adami C, Sorci G, Blasi E, Agneletti AL, Bistoni F, Donato R. S100B expression in and effects on microglia. Glia 2001; 33(2): 131-42.
[http://dx.doi.org/10.1002/1098-1136(200102)33:2<131:AID-GLIA1012>3.0.CO;2-D] [PMID: 11180510]
[7]
Schwieler L, Larsson MK, Skogh E, et al. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia--significance for activation of the kynurenine pathway. J Psychiatry Neurosci 2015; 40(2): 126-33.
[PMID: 25455350]
[8]
Fernandes BS, Steiner J, Bernstein HG, et al. C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications. Mol Psychiatry 2016; 21(4): 554-64.
[http://dx.doi.org/10.1038/mp.2015.87] [PMID: 26169974]
[9]
Solanki R, Singh P, Singh M, Sinha M, Swami MK, Saini S. C-reactive protein (CRP) in patients with schizophrenia: are they related with symptomatology? J Mental Health Human Behav 2010; 6: 1-5.
[PMID: 30364161]
[10]
Müller N, Myint A-M, Krause D, Weidinger E, Schwarz MJ. Anti-inflammatory treatment in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2013; 42: 146-53.
[http://dx.doi.org/10.1016/j.pnpbp.2012.11.008] [PMID: 23178230]
[11]
Löffler S, Löffler-Ensgraber M, Fehsel K, Klimke A. Clozapine therapy raises serum concentrations of high sensitive C-reactive protein in schizophrenic patients. Int Clin Psychopharmacol 2010; 25(2): 101-6.
[http://dx.doi.org/10.1097/YIC.0b013e32833643fd] [PMID: 20101184]
[12]
Diaz FJ, Pérez-Iglesias R, Mata I, et al. Possible effects of some antipsychotic drugs on C-reactive protein in a drug-naïve psychotic sample. Schizophr Res 2010; 121(1-3): 207-12.
[http://dx.doi.org/10.1016/j.schres.2010.06.002] [PMID: 20580206]
[13]
Henderson DC, Fan X, Copeland PM, et al. Aripiprazole added to overweight and obese olanzapine-treated schizophrenia patients. J Clin Psychopharmacol 2009; 29(2): 165-9.
[http://dx.doi.org/10.1097/JCP.0b013e31819a8dbe] [PMID: 19512978]
[14]
Stefanović V, Mihajlović G, Nenadović M, Đukić-Dejanović S, Borovčanin M, Trajković G. The effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia. Vojnosanitetski pregled 2015; 72(12): 1085-92.
[http://dx.doi.org/10.2298/VSP140526016S ]
[15]
Perez-Iglesias R, Mata I, Pelayo-Teran JM, et al. Glucose and lipid disturbances after 1 year of antipsychotic treatment in a drug-naïve population. Schizophr Res 2009; 107(2-3): 115-21.
[http://dx.doi.org/10.1016/j.schres.2008.09.028] [PMID: 18993033]
[16]
Migliardi G, Spina E, D’Arrigo C, et al. Short- and long-term effects on prolactin of risperidone and olanzapine treatments in children and adolescents. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33(8): 1496-501.
[http://dx.doi.org/10.1016/j.pnpbp.2009.08.009] [PMID: 19706318]
[17]
Ulrich S, Neuhof S, Braun V, Meyer FP. Therapeutic window of serum haloperidol concentration in acute schizophrenia and schizoaffective disorder. Pharmacopsychiatry 1998; 31(5): 163-9.
[http://dx.doi.org/10.1055/s-2007-979322] [PMID: 9832347]
[18]
Small JG, Hirsch SR, Arvanitis LA, Miller BG, Link CG. Seroquel Study Group. Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Arch Gen Psychiatry 1997; 54(6): 549-57.
[http://dx.doi.org/10.1001/archpsyc.1997.01830180067009] [PMID: 9193196]
[19]
Olesen OV. Therapeutic drug monitoring of clozapine treatment. Therapeutic threshold value for serum clozapine concentrations. Clin Pharmacokinet 1998; 34(6): 497-502.
[http://dx.doi.org/10.2165/00003088-199834060-00005] [PMID: 9646010]
[20]
Dufour A, Desanti C, Eds. Pharmacocinétique et métabolisme de l’amisulpride. Paris: Expansion Scientifique Publications 1988.
[21]
Sakurai Y, Nakahara T, Takahashi R. Prediction of response to chlorpromazine treatment in schizophrenics. Psychopharmacology (Berl) 1975; 44(2): 195-203.
[http://dx.doi.org/10.1007/BF00421010] [PMID: 1105634]
[22]
Duarte T, Barbisan F, do Prado-Lima PAS, et al. Ziprasidone, a second-generation antipsychotic drug, triggers a macrophage inflammatory response in vitro. Cytokine 2018; 106: 101-7.
[PMID: 29103822]
[23]
Meyer JM, Davis VG, Goff DC, et al. Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia Trial: prospective data from phase 1. Schizophr Res 2008; 101(1-3): 273-86.
[http://dx.doi.org/10.1016/j.schres.2007.12.487] [PMID: 18258416]
[24]
Meyer JM, McEvoy JP, Davis VG, et al. Inflammatory markers in schizophrenia: comparing antipsychotic effects in phase 1 of the clinical antipsychotic trials of intervention effectiveness study. Biol Psychiatry 2009; 66(11): 1013-22.
[http://dx.doi.org/10.1016/j.biopsych.2009.06.005] [PMID: 19640511]
[25]
Gurung J, Chamlagai D, Bera NK, Chaudhuri TK. Elevated levels of C-reactive protein and IL-6 among the antipsychotic medicating schizophrenia patients of Siliguri, West Bengal, India. Nord J Psychiatry 2018; 72(4): 311-7.
[PMID: 29464976]
[26]
Sopko MA, Caley CF. Chronic leukocytosis associated with clozapine treatment. Clin Schizophr Relat Psychoses 2010; 4(2): 141-4.
[http://dx.doi.org/10.3371/CSRP.4.2.6] [PMID: 20643637]
[27]
Sheldon J, Riches P, Gooding R, Soni N, Hobbs JR. C-reactive protein and its cytokine mediators in intensive-care patients. Clin Chem 1993; 39(1): 147-50.
[PMID: 8419041]
[28]
Orsolini L, Sarchione F, Vellante F, et al. Protein-C reactive as biomarker predictor of schizophrenia phases of illness? Curr Neuropharmacol 2018; 16(5): 583-606.
[http://dx.doi.org/10.2174/1570159X16666180119144538] [PMID: 29357805]
[29]
Song C. Lin Ah, Kenis G, Bosmans E, Maes M. Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist. Schizophr Res 2000; 42(2): 157-64.
[http://dx.doi.org/10.1016/S0920-9964(99)00116-4] [PMID: 10742653]
[30]
Maes M, Meltzer HY, Bosmans E. Immune-inflammatory markers in schizophrenia: comparison to normal controls and effects of clozapine. Acta Psychiatr Scand 1994; 89(5): 346-51.
[http://dx.doi.org/10.1111/j.1600-0447.1994.tb01527.x] [PMID: 8067274]
[31]
Maes M, Bosmans E, Kenis G, De Jong R, Smith RS, Meltzer HY. In vivo immunomodulatory effects of clozapine in schizophrenia. Schizophr Res 1997; 26(2-3): 221-5.
[http://dx.doi.org/10.1016/S0920-9964(97)00057-1] [PMID: 9323354]
[32]
da Cruz Jung IE, Machado AK, da Cruz IBM, et al. Haloperidol and risperidone at high concentrations activate an in vitro inflammatory response of RAW 264.7 macrophage cells by induction of apoptosis and modification of cytokine levels. Psychopharmacology (Berl) 2016; 233(9): 1715-23.
[http://dx.doi.org/10.1007/s00213-015-4079-7] [PMID: 26391290]
[33]
Baumeister D, Ciufolini S, Mondelli V. Effects of psychotropic drugs on inflammation: consequence or mediator of therapeutic effects in psychiatric treatment? Psychopharmacology (Berl) 2016; 233(9): 1575-89.
[http://dx.doi.org/10.1007/s00213-015-4044-5] [PMID: 26268146]
[34]
McNamara RK, Jandacek R, Rider T, Tso P. Chronic risperidone normalizes elevated pro-inflammatory cytokine and C-reactive protein production in omega-3 fatty acid deficient rats. Eur J Pharmacol 2011; 652(1-3): 152-6.
[http://dx.doi.org/10.1016/j.ejphar.2010.11.010] [PMID: 21118685]
[35]
Kegel ME, Bhat M, Skogh E, et al. Imbalanced kynurenine pathway in schizophrenia. Int J Trypto Res 2014; 7: 15-22.
[http://dx.doi.org/10.4137/IJTR.S16800]
[36]
Hess EV. Drug-related lupus. Curr Opin Rheumatol 1991; 3(5): 809-14.
[http://dx.doi.org/10.1097/00002281-199110000-00010] [PMID: 1751313]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 4
Year: 2019
Page: [261 - 266]
Pages: 6
DOI: 10.2174/2666082215666191018160333

Article Metrics

PDF: 14
HTML: 3
EPUB: 1
PRC: 1