IL-6 STIMULATION OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN (IGFBP)-1 PRODUCTION

TNF alpha and IL-1 beta have previously been shown to increase the IGF BP-1 concentration in plasma and liver under in vivo conditions. The p resent study demonstrates that another inflammatory cytokine, IL-6, al so elevates a 30- to 32-kDa IGF binding protein in the plasma of mice. Moreover, IL-6 produced dose- and time-dependent increases in IGFBP-1 production by HepGZ cells. The maximal IL-B-induced increase in IGFBP -1 was comparable to that observed with dexamethasone, and this increa se was attenuated by diltiazem or dantrolene, both of which are known to reduce the cytosolic Ca2+ concentration. Finally, incubation of Hep G2 cells with TNF alpha or IL-1 beta also increased IGFBP-1 in a dose- dependent manner. These results demonstrate that IGFBP-1 production is mediated directly by proinflammatory cytokines and suggest that this mechanism may be important for the upregulation of IGFBP-1 seen in cat abolic conditions associated with overexpression of these cytokines. ( C) 1996 Academic Press, Inc.