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-1α, IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α). Addition of saturating concentrations of neutralizing antibodies against IL-1α, IL-1β, or TNF-α into purified RSV-infected cell cultures resulted in a significant inhibition of IL-6 production, although anti-IL-1α antibody had the most predominant effect (80% inhibition). Anti-IL-1α antibody also almost completely blocked the expression of mRNA for IL-6. Addition of therapeutic concentrations of dexamethasone (1 μM) or ribavirin (90 μg/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.