lL - 8 induces T cell chemotaxis , suppresses lL - 4 , and up - regulates lL - 8 production by CD 4 T cells

Interleukin-8 (IL-8), a neutrophil-activatbig cytokine, also activates certain T cell functions such as chemotaxis. We additionally find (n 6) that recombinant (rIL-8; 1-100 ng/ml), when added to 24 h culture of human CD4 T cells, suppressed the spontaneous production of IL-4 (50-85%). Steady state production of IL-4 was typically around 30 pg/nil, determined by use of a solidphase immunoabsorbant assay. De novo synthesis of IL-4 from CD4’ T cells cultured for 3 days was also evaluated by use of detection of [355]methionine incorporalion, as visualized by autoradiography of 2-D gels, and showed that IL-8 suppressed IL-4 production. This suppression of IL-4 production was confirmed in the cytosol fraction by use ofWestern blotting. The effect of IL-8 (100 ngJml) was comparable to that of 10 ug/mi recombinant interferon-’)’, both strongly suppressing 11-4 production. The regulatory effect of IL-8 on IL-4 production was also indicated by the fact that addition of a neutralizing monoclonal antiIL-8 antibody (WS.4) enhanced the spontaneous IL-4 production when added to the cultures of CD4 T cells, thereby probably inactivating the effect of IL-8 originating from the cutured T cells. Also, we observed that IL-4 mRNA expression was downregulated when the CD4 T cells were cultured for 12 h in the presence of 100 ngJml IL-B. The suppression of IL-4 mRNA expression could be prevented by adding anti-IL-8 (20 .tg/ml) or IL-b (100 ng/ml) 1 h before adding rIL-8. Thus, IL-8 may be an important regulator of CD4 T cell-derived IL-4, thereby possibly regulating the balance between humoral and cellular T cell-dependent responses. J. Leukoc. BiOI. 59: 407-411; 1996.