Poly I:C-induced antiviral and cytotoxic activities are mediated by different mechanisms.
Macrophages play an important role in host defenses against tumors and virus infections by killing tumor or virus infected cells (extrinsic cytotoxicity) and by limiting virus replication within themselves (intrinsic antiviral activity). Since common macrophage products may be involved in both extrinsic cytotoxicity and intrinsic antiviral activity, we decided to investigate the mechanisms by which Poly I:C-activated macrophages resist infection with HSV-1 and inhibit the growth of tumor cells. The ability of macrophages to resist infection with HSV-1 or to inhibit growth of tumor cells was assessed following treatment with Poly I:C in the presence of antibodies to various cytokines or in the presence of inhibitors/scavengers of toxic macrophage products. Only antibodies to IFN-beta were able to abrogate the protective effects of Poly I:C in macrophages infected with HSV-1, suggesting that the antiviral activity induced by this immunomodulator was mediated by the production of IFN-beta, which acted in an autocrine manner. In contrast, anti-TNF-alpha, anti-IFN-alpha/beta anti-IFN-beta antibodies and inhibitors of nitric oxide and C1q production were all able to partially abrogate Poly I:C-induced cytostatic activity, suggesting that multiple mechanisms are involved in macrophage cytostasis. Our results indicate the Poly I:C-induced intrinsic antiviral and extrinsic cytotoxic activities are mediated by different mechanisms.
Department of Microbiology and Immunology, University of South Carolina, School of Medicine, Columbia 29208.
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S
Pyo
J D
JD
Gangemi
A
A
Ghaffar
E P
EP
Mayer
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D016898:Interferon-alpha / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D011070:Poly I-C / Q000494:pharmacology*; D018139:Simplexvirus / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000998:Antiviral Agents; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D011070:Poly I-C