Biologic response modifiers as antivirals in immunosuppressed hosts.
A wide variety of immunomodulators/biologic response modifiers (BRM) have been demonstrated to provide broad spectrum antiviral activity against both RNA and DNA viruses in several animal species. Dramatic decreases in mortality, reduced virus titers in tissues, and reduced histopathology can be produced. The antivirally effective agents include microbially derived materials, polyanions, cytokines, and chemically diverse small molecular weight chemicals. Antiviral efficacy with BRM treatment has been shown in numerous kinds of immunosuppression, emphasizing the potential for BRM treatment in immunocompromised patients. The greatest protective effects are observed with prophylactic or early therapeutic treatment. BRMs act indirectly, most likely by activating cells and/or inducing antiviral mediators early in the course of viral pathogenesis. In general, viral specific immune responses in BRM-treated and infected mice are absent or similar to those in untreated mice. Because BRMs are pleiotropic in their immunomodulatory effects, it has been difficult to establish whether one cell type or mediator is critical for the broad spectrum antiviral activity. Interferon appears to be critical for some small molecular weight synthetic compounds, but does not appear to explain all the antiviral activity of certain large molecular weight polyanions. Whether there is a unified antiviral mechanism among different BRMs remains to be determined.
Morahan
P S
PS
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129.
Pinto
A J
AJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D016867:Immunocompromised Host / Q000187:drug effects* / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D007155:Immunologic Factors; D007372:Interferons