Rhinovirus-Induced Oxidative Stress and Interleukin-8 Elaboration Involves p47-phox but Is Independent of Attachment to Intercellular Adhesion Molecule-1 and Viral Replication

Kaul, Poonam; Biagioli, Matthew C.; Singh, Inderjit; Turner, Ronald B.

Virus-induced elaboration of proinflammatory cytokines is mediated by virus-induced oxidative stress. The purpose of these studies was to determine the source of the virus-induced oxidative stress. Inhibition of viral replication with antibody to intercellular adhesion molecule-1 had no effect on virus-induced oxidative stress or interleukin-8 (IL-8) response (597 ± 88 vs. 668 ± 78 pg/mL in control cells). Treatment of cells with diphenylene iodonium inhibited virus-induced oxidative stress and IL-8 elaboration, but allopurinol, ibuprofen, and rotenone had no effect. Studies in cell lines produced from a patient with gp91-phox deficiency revealed normal responses. In contrast, the oxidative response was decreased and the IL-8 concentration was 227 ± 36 pg/mL in cells from a patient with p47-phox deficiency, compared with 664 ± 48 pg/mL in control cells. These studies suggest that the stimulation of reactive oxygen species by viral challenge occurs at the cell surface even in the absence of viral replication and involves a flavoprotein that may act in concert with p47-phox.