Autocrine regulation and experimental modulation of interleukin-6 expression by human pulmonary epithelial cells infected with respiratory syncytial virus

The mechanisms of regulation of interleukin-6 (IL-6) production in respiratory syncytial virus (RSV)-infected respiratory epithelial cells were evaluated in A549 cell cultures, Incubation with purified RSV resulted in significant production of IL-1 alpha IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha). Addition of saturating concentrations of neutralizing antibodies against IL-1 alpha, IL-1 beta, or TNF-alpha into purified RSV-infected cell cultures resulted in a significant inhibition of IL-6 production, although anti-ll-la antibody had the most predominant effect (80% inhibition), Anti-IL-1 alpha antibody also almost completely blocked the expression of mRNA for IL-6, Addition of therapeutic concentrations of dexamethasone (1 mu M) or ribavirin (90 mu g/ml), an antiviral agent, also significantly inhibited the synthesis of IL-6. Hence, in clinical settings, pharmacological agents such as the specific antagonists of IL-6-inducing cytokines, as well as dexamethasone and ribavirin, could be used to modulate IL-6 production.