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-1alpha, IL-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha). Addition of saturating concentrations of neutralizing antibodies against IL-1alpha, IL-1beta, or TNF-alpha into purified RSV-infected cell cultures resulted in a significant inhibition of IL-6 production, although anti-IL-1alpha antibody had the most predominant effect (80% inhibition). Anti-IL-1alpha antibody also almost completely blocked the expression of mRNA for IL-6. Addition of therapeutic concentrations of dexamethasone (1 microM) or ribavirin (90 microg/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.
Jiang
Z
Z
Department of Pediatrics, Children's Hospital at University of Texas Medical Branch, Galveston 77555, USA.
Kunimoto
M
M
Patel
J A
JA
D000998:Antiviral Agents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000166:cytology; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects / Q000502:physiology*; D012254:Ribavirin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000998:Antiviral Agents; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D012254:Ribavirin; D003907:Dexamethasone