IL-10 AND IL-4 SYNERGIZE WITH TNF-ALPHA TO INDUCE IL-1RA PRODUCTION BY HUMAN NEUTROPHILS

The anti-inflammatory properties of IL-4, IL-10, IL-13 and TGF-beta ar e associated with their ability to repress the production of pro-infla mmatory cytokines and to favour the release of interleukin-1 receptor antagonist (IL-1ra). Here, we investigate their actions on activated h uman polymorphonuclear cells (PMN), IL-4 and TGF-beta were able to inc rease the production of IL-1ra, however only IL-4 were able to further increase IL-1ra production in the presence of LPS. When IL-1ra produc tion by PMN was induced by tumour necrosis factor-alpha (TNF-alpha), I L-10 and IL-4 both amplified its release and its presence as a cell-as sociated form, In conclusion, IL-10 which was unable to induce IL-1ra by itself or to amplify the LPS-induced production by PMN, was able to increase its release when TNF-alpha, is the triggering signal, IL-4 w as active in the different combinations tested; IL-13 and TGF-beta did not further modulate LPS- and TNF-alpha-induced IL-1ra production by PMN. (C) 1996 Academic Press Limited