EFFECTS OF CLOZAPINE ON PLASMA CYTOKINE AND SOLUBLE CYTOKINE RECEPTORLEVELS

The antipsychotic drug clozapine frequently induces fever during the f irst weeks of administration. In addition, it has been shown that cloz apine increases plasma soluble interleukin-2 receptor (sIL-2r) levels as early as 1 week after treatment is started. These findings suggest that clozapine has immunomodulatory effects. To investigate this issue in more detail, we assessed the time course of rectal temperature, bl ood cell counts, and cytokine and soluble cytokine receptor plasma lev els during 6 weeks of clozapine treatment in 27 schizophrenic patients . Clozapine increased the plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors p55 and p75, and sIL-2r. These inc reases were independent of prior or concurrent medication and did also occur in patients who did not experience clozapine-induced fever. How ever, increases in TNF-alpha and sIL-2r levels were more pronounced in patients with clozapine-induced fever who showed in addition increase d plasma IL-6 levels and granulocyte counts. Plasma IL-1 receptor anta gonist levels and monocyte and lymphocyte counts were not affected by clozapine treatment. It is concluded that clozapine has consistent in vivo immunomodulatory effects. The results presented suggest that cloz apine-induced fever is mediated by pyrogenic cytokines.