Cytomegalovirus induction of interleukin-6 in lung fibroblasts occurs independently of active infection and involves a G protein and the transcription factor, NF-kappa B

Cytomegalovirus (CMV) infection induces the proinflammatory cytokine, inter leukin (IL)-6, which may contribute to the pathology of the infection. In v itro CMV induction of IL-6 by human lung fibroblasts was studied. The quant ity of cytokine in culture supernatants was maximal 20 h after infection an d decreased thereafter. Transcription of the IL-6 gene and IL-6 protein exp ression were equally stimulated by infectious and W-inactivated virus (CMV- UV), CMV-W-stimulated IL-6 was inhibited by pyrrolidinedithiocarbamate (an inhibitor of the transcription factor, NF-kappa B) and by pertussis toxin ( suggesting the involvement of a G protein) and occurred in the absence of C MV immediate-early antigen transcription. Neutralizing antibodies to IL-1 b eta or tumor necrosis factor-alpha did not affect CMV-W-induced IL-6, but e xpression was inhibited by antibody to the CMV attachment glycoprotein, IL- 6 production by fibroblasts occurs independently from productive infection but has characteristics that suggest a ligand receptor-mediated pathway. Th is function may be important in pathology or disease resolution.