Immunologic variables in acute mania of bipolar disorder.

Macrophages, lymphocytes and their products, may be involved in the pathophysiology of psychiatric disorders. The cell-mediated immune activation response of manic patients during pre-medication and medication stages remains unclear. The purpose of this case-control study was to investigate the plasma levels of immunologic variables, including interleukin (IL)-1 receptor antagonist (IL-1RA), soluble CD 4 (sCD4) and sCD8, and TH1 (interferon [IFN]-gamma and IL-2) and TH2 (IL-4 and IL-10) cytokines in patients with pre-medicated, medicated bipolar mania. The study subjects, aged 16-44 years, were physically healthy patients with Young Mania Rating Scale (YMRS) scores > or =26, and normal controls, aged 19-40 years, were matched for sex. The immune variables were measured in acute mania and in consequent remission (YMRS scores < or =12) among bipolar patients. The plasma levels of IL-1RA, sCD4, and sCD8 were found significantly increased in pre-medicated acute manic patients as compared to normal controls. But only IL-1RA and sCD8 were found different in remitted bipolar patients as compared to normal controls. For TH1 cytokines, culture supernatant level of IFN-gamma was found significantly lower in manic patients of both acute and remission stages as compared to normal controls. No significant difference was found in IL-2 level in pre-medicated acute manic patients compared to controls. For TH2 cytokines, no significant differences in IL-4 and IL-10 levels were observed. We showed that cell-mediated immune response was activated in patients with bipolar disorder during the pre-medication, medication, and the remission stages. Our study findings suggest that the immune-modulation in patients with bipolar disorder may be abnormal.

Reduced production of interferon-gamma but not interleukin-10 in bipolar mania and subsequent remission.

BACKGROUND: Activation of inflammatory response system (IRS) is suggested by increased levels of plasma soluble interleukin-2 receptor (sIL-2R) in patients with bipolar mania. The reasons for changes in stimulated interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) production in bipolar mania along with subsequent remission remain unclear. METHODS: We measured phytohemagglutinin (PHA)-stimulated IFN-gamma and IL-10 production in 20 physically healthy inpatients aged between 18 and 45 years with bipolar mania (DSM-IV) using Young Mania Rating Scale (YMRS) scores > or = 26 and in subsequent remission (YMRS < or = 12), as well as in 15 age- and sex-matched healthy normal controls. RESULTS: The mean values of IFN-gamma production in patients in acute mania and in subsequent remission were significantly lower than those of healthy controls (P=0.0004, P=0.0005, respectively). There was no significant difference in IL-10 production between bipolar patients in acute mania as well as in subsequent remission and healthy controls. In acute mania, the mean values of IFN-gamma and IL-10 production in medicated patients (n = 13) did not differ from those of drug-free patients (n = 7). Other clinical variables had no effect on IFN-gamma and IL-10 production. LIMITATION: The uncontrolled medication, small sample size of the bipolar individuals, and some immune re-measurements prior to full remission periods, limit generalization from the data in this study. CONCLUSION: Reduced production of IFN-gamma without alternation of IL-10 in bipolar mania and subsequent remission suggest that the immune modulation may vary in patients with different major psychiatric disorders.