Immunological Dysfunction in Schizophrenia: A Systematic Approach

Abstract

Background: In the present study, immunological alterations were investigated as one possible factor contributing towards the pathogenesis of schizophrenia. Specifically cellular changes, deviating cytokine production and interfering variables were studied in order to improve our understanding of how these factors interact. Method: 44 acutely ill schizophrenics were compared with matched healthy controls. Cell numbers were determined by flow cytometry and cytokine production by whole blood assay and ELISA. A criss-cross technique was employed for the assessment of interfering serum factors. Results: Cell counts for leukocytes, lymphocytes, pan T cells, activated T cells and the absolute B cell count of the schizophrenic patients were all within normal limits. The absolute and relative monocyte counts, the number of IL-2 receptor carrying T cells and the relative B cell count were slightly elevated. IL-2 and IFN-γ production were increased while IL-10 production, the sIL-2R and cortisol levels remained unchanged. No interfering serum factors were detected. Conclusion: The deficient production of TH-1 cytokines in schizophrenia is not due either to a changed number of immunocompetent cells or to a counterregulation of the TH-2 cytokine IL-10. Serum factors in in vitro testing are not responsible for the deficient cytokine production.

Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment

“…75 By employing a 'criss-cross' technique, we found no significant influence of the sera of medicated schizophrenic subjects on IL-2-or IFN-␥ production by lymphocytes from normal individuals. 68 Hence the notion of a major in vivo influence by neuroleptic medication is not strongly supported by current findings, but can also not be completely ruled out.…”

“…15 No differences were found in an extensive analysis of cell counts for leukocytes, lymphocytes, pan T cells, activated T cells and absolute numbers of B cells; however, a slight elevation of CD3/CD25+ cells carrying the IL-2 receptor and absolute/relative monocyte counts could be detected. 68 (b) In earlier studies we reported that there was also no evidence for an influence of IL-4 15 or IL-10 29 on cytokine production. The production of IL-10 was in fact lowered in schizophrenia, 29 a finding which even suggests a malfunction in the physiological antagonism between the TH-1 and the TH-2 systems.…”

Implication of the env Gene of the Human Endogenous Retrovirus W Family in the Expression of BDNF and DRD3 and Development of Recent-Onset Schizophrenia

“…3 There are various hypotheses on the mechanisms of schizophrenia, 3,[33][34][35][36] such as dopamine hypothesis, 34 neurodevelopmental hypothesis, 35 autoimmune hypothesis, 36 etc. But the recent convergence of neuropathologic, neurotransmitter, and genetic studies indicates that there is still a long way to understanding the molecular causes of schizophrenia.…”

The plasma levels of interleukin-12 in schizophrenia, major depression, and bipolar mania: effects of psychotropic drugs

“…6 The innate immune activation in schizophrenia has been based on the findings of increased monocyte numbers, increased activity of macrophage, increased proinflammatory cytokine levels such as IL-1, IL-6, IL-18 and tumor necrosis factor(TNF)-␣. [7][8][9][10][11] Schizophrenia is also characterized by a decrease in IL-2 production [12][13][14] and interferon(IFN)-␥, 7,15 traditionally classified as Th1 cytokines, and an increase in IL-4 16 and IL-10, 17,18 traditionally classified as Th2 cytokines. On the other hand, there have been reports of an increased Th1 system in schizophrenia, specifically an increased IL-2 level in plasma 19 and in cerebrospinal fluid 20,21 and increased production of IL-2 and IFN-␥.…”