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. 2001 Jun;10(3):109–115. doi: 10.1080/09629350123895

Serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha in schizophrenic patients, relation with symptomatology and responsiveness to risperidone treatment.

A B Erbağci 1, H Herken 1, O Köylüoglu 1, N Yilmaz 1, M Tarakçioglu 1
PMCID: PMC1781702  PMID: 11545247

Abstract

Activation of the inflammatory response system and varied levels of cytokines in acute schizophrenia have been suggested by recent studies. Psychopharmacologic agents can differentially effect cytokine production, which suggests that therapeutic function of neuroleptics may involve immunomodulation. The present study was carried out to examine: (i) serum concentrations of interleukin (IL)-1beta, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8 and tumour necrosis factor (TNF)-alpha in schizophrenic patients; (ii) their relation with psychopathological assessment; and (iii) the relation of the initial cytokine levels with responsiveness to risperidone therapy. Thirty-four drug-free schizophrenic patients with acute exacerbation and 23 age- and gender-matched healthy controls were recruited for this study. Psychopathological assessments at admission and throughout risperidone treatment for 60 days were recorded. Serum cytokine concentrations were determined with chemilumunescence assays. According to our results, serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha concentrations adjusted for age, gender, body mass index and smoking were no different in patients with schizophrenia and controls and among subtypes of schizophrenia. However, the initial TNF-alpha concentrations had a significant effect on Brief Psychiatric Rating Scale and Scale Assessment of Positive Symptoms scores. The initial cytokine concentrations of the patients responsive to risperidone were not significantly different from those of non-responsive patients. The present study demonstrates that plasma levels of IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha adjusted for confounding factors are not altered in drug-free schizophrenic patients at acute exacerbation. We suggest that, if cytokine production is altered in schizophrenia, these alterations may not be detectable in systemic circulation. According to our results, the therapeutic effect of risperidone is not related to basal levels of the aforementioned cytokines. However, serum TNF-alpha may contribute to symptomatology in schizophrenia

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Selected References

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  1. Arolt V., Rothermundt M., Wandinger K. P., Kirchner H. Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment. Mol Psychiatry. 2000 Mar;5(2):150–158. doi: 10.1038/sj.mp.4000650. [DOI] [PubMed] [Google Scholar]
  2. Baker I., Masserano J., Wyatt R. J. Serum cytokine concentrations in patients with schizophrenia. Schizophr Res. 1996 May;20(1-2):199–203. doi: 10.1016/0920-9964(95)00089-5. [DOI] [PubMed] [Google Scholar]
  3. Barak V., Barak Y., Levine J., Nisman B., Roisman I. Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of schizophrenic patients. J Basic Clin Physiol Pharmacol. 1995;6(1):61–69. doi: 10.1515/jbcpp.1995.6.1.61. [DOI] [PubMed] [Google Scholar]
  4. Cazzullo C. L., Scarone S., Grassi B., Vismara C., Trabattoni D., Clerici M., Clerici M. Cytokines production in chronic schizophrenia patients with or without paranoid behaviour. Prog Neuropsychopharmacol Biol Psychiatry. 1998 Aug;22(6):947–957. doi: 10.1016/s0278-5846(98)00059-1. [DOI] [PubMed] [Google Scholar]
  5. Ganguli R., Brar J. S., Chengappa K. R., DeLeo M., Yang Z. W., Shurin G., Rabin B. S. Mitogen-stimulated interleukin-2 production in never-medicated, first-episode schizophrenic patients. The influence of age at onset and negative symptoms. Arch Gen Psychiatry. 1995 Aug;52(8):668–672. doi: 10.1001/archpsyc.1995.03950200058014. [DOI] [PubMed] [Google Scholar]
  6. Ganguli R., Rabin B. S., Belle S. H. Decreased interleukin-2 production in schizophrenic patients. Biol Psychiatry. 1989 Aug;26(4):427–430. doi: 10.1016/0006-3223(89)90061-9. [DOI] [PubMed] [Google Scholar]
  7. Ganguli R., Rabin B. S. Increased serum interleukin 2 receptor concentration in schizophrenic and brain-damaged subjects. Arch Gen Psychiatry. 1989 Mar;46(3):292–292. doi: 10.1001/archpsyc.1989.01810030098018. [DOI] [PubMed] [Google Scholar]
  8. Gaughran F., O'Neill E., Cole M., Collins K., Daly R. J., Shanahan F. Increased soluble interleukin 2 receptor levels in schizophrenia. Schizophr Res. 1998 Feb 9;29(3):263–267. doi: 10.1016/s0920-9964(97)00099-6. [DOI] [PubMed] [Google Scholar]
  9. Haack M., Hinze-Selch D., Fenzel T., Kraus T., Kühn M., Schuld A., Pollmächer T. Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res. 1999 Sep-Oct;33(5):407–418. doi: 10.1016/s0022-3956(99)00021-7. [DOI] [PubMed] [Google Scholar]
  10. Katila H., Hänninen K., Hurme M. Polymorphisms of the interleukin-1 gene complex in schizophrenia. Mol Psychiatry. 1999 Mar;4(2):179–181. doi: 10.1038/sj.mp.4000483. [DOI] [PubMed] [Google Scholar]
  11. Kim Y. K., Kim L., Lee M. S. Relationships between interleukins, neurotransmitters and psychopathology in drug-free male schizophrenics. Schizophr Res. 2000 Sep 1;44(3):165–175. doi: 10.1016/s0920-9964(99)00171-1. [DOI] [PubMed] [Google Scholar]
  12. Kronfol Z., Remick D. G. Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry. 2000 May;157(5):683–694. doi: 10.1176/appi.ajp.157.5.683. [DOI] [PubMed] [Google Scholar]
  13. Lin A., Kenis G., Bignotti S., Tura G. J., De Jong R., Bosmans E., Pioli R., Altamura C., Scharpé S., Maes M. The inflammatory response system in treatment-resistant schizophrenia: increased serum interleukin-6. Schizophr Res. 1998 Jun 22;32(1):9–15. doi: 10.1016/s0920-9964(98)00034-6. [DOI] [PubMed] [Google Scholar]
  14. Maes M., Bosmans E., Calabrese J., Smith R., Meltzer H. Y. Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers. J Psychiatr Res. 1995 Mar-Apr;29(2):141–152. doi: 10.1016/0022-3956(94)00049-w. [DOI] [PubMed] [Google Scholar]
  15. Maes M., Bosmans E., Kenis G., De Jong R., Smith R. S., Meltzer H. Y. In vivo immunomodulatory effects of clozapine in schizophrenia. Schizophr Res. 1997 Aug 29;26(2-3):221–225. doi: 10.1016/s0920-9964(97)00057-1. [DOI] [PubMed] [Google Scholar]
  16. Maes M., Bosmans E., Ranjan R., Vandoolaeghe E., Meltzer H. Y., De Ley M., Berghmans R., Stans G., Desnyder R. Lower plasma CC16, a natural anti-inflammatory protein, and increased plasma interleukin-1 receptor antagonist in schizophrenia: effects of antipsychotic drugs. Schizophr Res. 1996 Jul;21(1):39–50. doi: 10.1016/0920-9964(96)00029-1. [DOI] [PubMed] [Google Scholar]
  17. Maes M., Meltzer H. Y., Buckley P., Bosmans E. Plasma-soluble interleukin-2 and transferrin receptor in schizophrenia and major depression. Eur Arch Psychiatry Clin Neurosci. 1995;244(6):325–329. doi: 10.1007/BF02190412. [DOI] [PubMed] [Google Scholar]
  18. Monteleone P., Fabrazzo M., Tortorella A., Maj M. Plasma levels of interleukin-6 and tumor necrosis factor alpha in chronic schizophrenia: effects of clozapine treatment. Psychiatry Res. 1997 Jun 16;71(1):11–17. doi: 10.1016/s0165-1781(97)00036-x. [DOI] [PubMed] [Google Scholar]
  19. Müller N., Empl M., Riedel M., Schwarz M., Ackenheil M. Neuroleptic treatment increases soluble IL-2 receptors and decreases soluble IL-6 receptors in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 1997;247(6):308–313. doi: 10.1007/BF02922260. [DOI] [PubMed] [Google Scholar]
  20. Naudin J., Capo C., Giusano B., Mège J. L., Azorin J. M. A differential role for interleukin-6 and tumor necrosis factor-alpha in schizophrenia? Schizophr Res. 1997 Aug 29;26(2-3):227–233. doi: 10.1016/s0920-9964(97)00059-5. [DOI] [PubMed] [Google Scholar]
  21. Prolo P., Licinio J. Cytokines in affective disorders and schizophrenia: new clinical and genetic findings. Mol Psychiatry. 1999 Mar;4(2):109–111. doi: 10.1038/sj.mp.4000523. [DOI] [PubMed] [Google Scholar]
  22. Rothermundt M., Arolt V., Leadbeater J., Peters M., Rudolf S., Kirchner H. Cytokine production in unmedicated and treated schizophrenic patients. Neuroreport. 2000 Oct 20;11(15):3385–3388. doi: 10.1097/00001756-200010200-00024. [DOI] [PubMed] [Google Scholar]
  23. Shintani F., Kanba S., Maruo N., Nakaki T., Nibuya M., Suzuki E., Kinoshita N., Yagi G. Serum interleukin-6 in schizophrenic patients. Life Sci. 1991;49(9):661–664. doi: 10.1016/0024-3205(91)90112-o. [DOI] [PubMed] [Google Scholar]
  24. Villemain F., Chatenoud L., Galinowski A., Homo-Delarche F., Ginestet D., Loo H., Zarifian E., Bach J. F. Aberrant T cell-mediated immunity in untreated schizophrenic patients: deficient interleukin-2 production. Am J Psychiatry. 1989 May;146(5):609–616. doi: 10.1176/ajp.146.5.609. [DOI] [PubMed] [Google Scholar]
  25. Wilke I., Arolt V., Rothermundt M., Weitzsch C., Hornberg M., Kirchner H. Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients. Eur Arch Psychiatry Clin Neurosci. 1996;246(5):279–284. doi: 10.1007/BF02190280. [DOI] [PubMed] [Google Scholar]
  26. Xu H. M., Wei J., Hemmings G. P. Changes of plasma concentrations of interleukin-1 alpha and interleukin-6 with neuroleptic treatment for schizophrenia. Br J Psychiatry. 1994 Feb;164(2):251–253. doi: 10.1192/bjp.164.2.251. [DOI] [PubMed] [Google Scholar]
  27. Zalcman S., Murray L., Dyck D. G., Greenberg A. H., Nance D. M. Interleukin-2 and -6 induce behavioral-activating effects in mice. Brain Res. 1998 Nov 16;811(1-2):111–121. doi: 10.1016/s0006-8993(98)00904-4. [DOI] [PubMed] [Google Scholar]
  28. van Kammen DP, McAllister-Sistilli CG, Kelley ME, Gurklis JA, Yao JK. Elevated interleukin-6 in schizophrenia. Psychiatry Res. 1999 Oct 11;87(2-3):129–136. doi: 10.1016/s0165-1781(99)00053-0. [DOI] [PubMed] [Google Scholar]

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