| Schizophrenia-a severe mental disease, as its Complex etiology and the heavy social burdens is paid more and more attention by the researchers, but the Pathogenic mechanism is still unknown. In recent years, many studies have found the changes of the serum cytokines in schizophrenia patients, and the unbalance of the Thl and Th2 function which is result from the changes of the Thl and Th2 cytokines in schizophrenia patients'immune system, as a result researchers are paying more and more attentions to the hypothesis of imbalance among the Neuro-endocrine-immune system. In this study, we aimed to know the changes of the serum IL-2,IL-4,IL-6 and TNF-a level in schizophrenia patients, and discovery the alternation of Thl and Th2 function of schizophrenia, then provide the convincing proof to the pathogenic mechanism of schizophrenia.ObjectiveDetect the alternation of Thl cytokines (IL-2,TNF-a) and Th2 cytokines (IL-4,IL-6) in immune system of schizophrenia, compare the variation of their Thl and Th2 function. Find the relation ships between the level of patients'cytokines and the character of patients.MethodCase-control study was used in this study, Subjects of patients group were chosen from Chang Chun Mental Health hospital from December 2009 to December 2010, patients who were admitted to this group were definitely diagnosed to have schizophrenia,150 subjects were chosen in to this group (79 patients were drug-naive,71 patients were at least 4 months drug-free). Diagnostic criteria:All patients must meeting the International Classification of Diseases-10th Revision (ICD-10) for schizophrenia, and consult the Chinese Classification and diagnosis of Mental Disorder-2-Revisation (CCMD-2-R). all patients were diagnosed by at least two psychiatrists, and were given the clinical classification. The 150 health controls who had done physical examination in The First Bethune Hospital of Jilin University, were matched with patients in the sex and age. Subjects with chronic or acute disease, infection, or past history of autoimmune disorder were excluded. Draw blood about 5ml, and collect the serum, Radioimmunoassay (RIA) was used to detect the serum level of IL-2,IL-4,IL-6 and TNF-a.Results1. Distribution of subjects'characters in the studyIn this study we use chi-square (X2) test to compare the distribution of subjects' characters in the questionnaire. As a result, there is no significant difference in composition of neither the composition of age nor gender between schizophrenia patients and control group (P>0.05). In the schizophrenia patients group, there is no significant difference in the distribution of subtype of illness, character before illness between male and female patients (p>0.05).2. Study of cytokine level in schizophrenia patients and health controlsThe results from this study show that:there is a significant difference between two groups (P<0.01), serum level of IL-2 and IL-6 is significantly higher than that of the health controls (P<0.01), while serum level of IL-4 and TNF-a is significantly lower than that of the health controls (P<0.01), in male subjects, there is no significant difference in the level of TNF-a between patients and control groups (P>0.05), in female subjects, the level of TNF-a in patients is lower than that of control groups (t=6.147, P<0.01), Level of TNF-a level in Hebephrenic type schizophrenia patients is higher than that of the other subtype patients (P<0.05); there is no significant difference in serum IL-2,IL-4 and IL-6 level between first and not first onset patients, while we find serum TNF-a level in first onset patients is significantly lower than that of the not first onset patients (t=2.206, P=0.029); We also find elevated serum IL-2 level in smoking patients (t=2.000,P=0.047), while there is no significant difference in the other cytokine of respective groups. In patient group the course of illness, age, age of first onset and character before illness can not affect the level of patients'cytokine.3. Variation of the Thl and Th2 function in subjectsIn this study, the ratio of Thl/Th2 in immune system is replaced by the ratio of IL-2/IL-4, as IL-2 is one of the major Thl related pro-inflammatory cytokine and IL-4 is one of the Th2 specific anti-inflammatory cytokine. We use the ratio of Thl/Th2 to represent the function of Thl/Th2, and then compare the ratio between the patients and controls. The result shows that:the ratio of Thl/Th2 in schizophrenia patients is significantly higher than that of the controls (t=13.378, P<0.001), it warns us the function of Thl and Th2 are imbalance with a shift to the function of Thl.ConclusionsSerum level of IL-2 and IL-6 are significantly higher than that of the health controls (P<0.01), while serum level of IL-4 and TNF-a are significantly lower than that of the health controls (P<0.01), and the lower of TNF-a level in patients may cause of the gender. The function of Thl and Th2 are imbalance in schizophrenia patients, with a shift to the function of Thl system. There are differences in the serum level of TNF-a in groups sorted by patients'general characters, these findings suggest that:gender, first onset or not, positive/negative family history, acute/chronic patients, different age groups, disease subtypes, character before illness may intimated associated with serum TNF-a of patients. The correlation ship of IL-6 with TNF-a, IL-2 with course of disease, and the disappearance of the correlation ship between IL-6 and age of subjects in schizophrenia patients suggest that:the inflammatory effect mediated by pro-inflammatory cytokine may play most important role in the pathogenesis of schizophrenia, and smoking may differ the function of immune system of schizophrenia patients.
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