Rhinovirus-induced oxidative stress and interleukin-8 elaboration involvesp47-phox but is independent of attachment to intercellular adhesion molecule-1 and viral replication

Virus-induced elaboration of proinflammatory cytokines is mediated by virus -induced oxidative stress. The purpose of these studies was to determine th e source of the virus-induced oxidative stress. Inhibition of viral replica tion with antibody to intercellular adhesion molecule-1 had no effect on vi rus-induced oxidative stress or interleukin-8 (IL-8) response (597 +/- 88 v s. 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 concentrat ion 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 th e cell surface even in the absence of viral replication and involves a flav oprotein that may act in concert with p47-phox.