N-FORMYL-METHIONYL-LEUCYL-PHENYLALANINE INDUCES AND MODULATES IL-1 AND IL-6 IN HUMAN PBMC

N-formyl-methionyl-leucyl-phenylalanine (fMLP), a bacterial derivative , induces and modulates various cellular responses linked to inflammat ion. In this work we evaluated the impact of fMLP stimulation on three pro-inflammatory cytokines: IL-1 alpha, IL-1 beta and IL-6, We found that MLP induces the secretion of IL-1 alpha, IL-1 beta and IL-6 in hu man peripheral blood mononuclear cells (PBMC), It also increased LPS-i nduced secretion of these three cytokines. Northern blot analysis demo nstrated that fMLP induced IL-1 alpha, IL-1 beta and IL-6 gene express ion by human PBMC, The fMLP-induced IL-1 alpha and IL-1 beta gene expr ession and IL-6 secretion were abolished by pertussis toxin pretreatme nt, which suggests that the fMLP induction of cytokine was also mediat ed via a G(i) protein, The concentration range of fMLP used to obtain these effects, in a dose dependent fashion, was 20 mu M to 1100 mu M. The mechanism by which fMLP modulates cytokine secretion is still not characterized, fMLP seems to share similar biological activities with other chemotactic factors (C5a, MCP-1, PAF, IL-8) that are able to mod ulate cytokines, and whose receptors belong to the same superfamily as the fMLP receptor(s). (C) 1996 Academic Press Limited