IL-4 DOWN-REGULATES IL-2-INDUCED, IL-3-INDUCED, AND GM-CSF-INDUCED CYTOKINE GENE-EXPRESSION IN PERIPHERAL-BLOOD MONOCYTES

IL-4, a product of the T-helper 0 (Th0) and 2 (Th2) subset, was origin ally described as a B-cell stimulatory factor and has subsequently bee n found to suppress IL-1 alpha, IL-1 beta, IL-6, IL-8, and TNF-alpha g ene expression in monocytes stimulated with LPS, and to upregulate IL- 1 receptor antagonist (IL1-RA) gene expression. In this study we inves tigated the effect of IL-4 on the expression of cytokine genes in mono cytes evoked by other T-helper cell cytokines: IL-2, IL-3, and GM-CSF. IL-4 down-regulated mRNA accumulation of the proinflammatory cytokine s IL-1 beta, IL-8, and TNF-alpha in monocytes stimulated with IL-2, IL -3, and GM-CSF. IL-4 also suppressed the IL-2-induced IL-6 mRNA expres sion. Temporal analysis of the IL-4 down-regulatory effect on the IL-2 -, IL-3-, or GM-CSF-induced proinflammatory cytokine gene expression i n monocytes provided evidence that IL-4 acts predominantly on the post -transcriptional level. This was supported by the observation that the down-regulatory capacity of IL-4 appeared to be dependent on de novo protein synthesis. IL-4 did not exert significant influence on the ind uction of expression of IL-1-RA or various CSFs by IL-2, IL-3, and GM- CSF. We hypothesize that owing to its being a down-regulator of the ex pression of proinflammatory cytokines induced by IL-2, IL-3, and GM-CS F products of activated Th0 or Th1 cells - together with its capacity as a B-cell stimulatory factor, IL-4 has an important role in directin g the immune response.