Interleukin 1 receptor antagonist production in human monocytes is induced by IL-1α, IL-3, IL-4 and GM-CSF
Abstract Interleukin 1 receptor antagonist (IL-1ra) is induced in monocytes stimulated with lipopolysaccharide (LPS) or cultured on adherent immunoglobulin G (IgG). We examined the effects of various cytokines on monocyte IL-1ra protein production and compared it to IL-1β, which is regulated differently. IL-3 and GM-CSF induced near equivalent amounts of IL-1ra protein as does LPS. IL-1α and IL-4 were weaker inducers. IL-3 and GM-CSF did not affect LPS or IgG induction of IL-1ra or LPS-induced IL-1β. However, our data confirmed that IL-4 up-regulated LPS-induced IL-1ra and down-regulated LPS-induced IL-1β. The kinetics of IL-1ra production by monocytes varied between stimulation with adherent IgG and cytokines or LPS. Cells cultured on adherent IgG exhibited a higher level of and more prolonged IL-1ra production. Relative IL-1ra mRNA levels after 8 h were in the order: adherent IgG LPS or GM-CSF IL-1α, IL-3 or IL-4. The following cytokines failed to induce IL-1ra production: IL-2, IL-6, G-CSF, M-CSF, IFN-γ, TGFβ 1 , TGFβ 2 , TNFα, acidic and basic FGF, PDGF and EGF. These results suggest that IL-1α, IL-3, IL-4 and GM-CSF may play important roles in regulating monocyte IL-1ra production and that different mechanisms may be involved in induction of IL-1ra by adherent IgG in comparison to LPS or other cytokines.