TNF-alpha and IL-1beta cross-desensitization of astrocytes and astrocytoma cell lines

Exposure of human astrocytes and astrocytoma cell lines to TNF-alpha, IL-1beta and gammaIFN induce expression of a specific member of the intercrine/chemokine family of cytokines, RANTES. Pre-incubation with non-stimulatory concentrations of TNF-alpha inhibit IL-1beta-stimulated RANTES expression and similarly, non-stimulatory concentrations of IL-1beta inhibits TNF-alpha induced RANTES expression. The lowered responsiveness of these cells is stably maintained for at least 24 h. The inhibitory effect of TNF-alpha on IL-1beta-induced responses was mediated by TNF receptor-1 since low concentrations of a specific anti-TNF receptor-1 antiserum mimicked the inhibitory effect. These results indicate that TNF and IL-1 receptors mediate pro- and antiinflammatory responses in a concentration dependent manner, suggesting that at low receptor occupancy, TNF and IL-1 receptors may share a common signaling pathway and behave as endogenous antiinflammatory cytokines.