IL-8 induces T cell chemotaxis, suppresses IL-4, and up-regulates IL-8 production by CD4(+) T cells

Interleukin-8 (IL-8), a neutrophil-activating 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/ml, determined by use of a solid- phase immunoabsorbant assay, De novo synthesis of IL-4 from CD4(+) T cells cultured for 3 days was also evaluated by use of detection of [S-35]methionine incorporation, 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 of Western blotting, The effect of IL-8 (100 ng/ml) was comparable to that of 10 ng/ml recombinant interferon-gamma, both strongly suppressing IL-4 production, The regulatory effect of IL-8 on IL-4 production was also indicated by the fact that addition of a neutralizing monoclonal anti-IL-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 ng/ml IL-8. The suppression of IL-4 mRNA expression could be prevented by adding anti-IL-8 (20 mu g/ml) or IL-10 (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.