Role of interferon-gamma in murine cytomegalovirus infection.
Interferon-gamma has well-documented antiviral and immunomodulatory activity, but its role in the control of cytomegalovirus (CMV) infection is not well studied. In a mouse model of murine CMV (MCMV) disease, interferon-gamma concentrations in serum but not in bronchoalveolar lavage fluid increased in response to viral infection. Serum interferon-gamma levels peaked at day 2 in the relatively resistant C57BL/6 mice, and, in contrast, did not peak until day 6 in susceptible BALB/c mice. Mice genetically lacking interferon-gamma (GKO) were more susceptible to MCMV, although strain differences persisted, with C57BL/6 GKO mice experiencing less severe MCMV disease than BALB/c GKO mice. Treatment of MCMV-infected BALB/c mice with exogenous interferon-gamma starting 2 days after viral infection had a modest protective effect at lower interferon-gamma doses (10(4) units), but interferon-gamma therapy markedly increased morbidity and mortality when higher doses (10(5) units) were used. We conclude that interferon-gamma plays a significant role in host response to MCMV and that the cytokine has dose- and time-dependent beneficial and adverse effects.
Pomeroy
C
C
Department of Medicine, University of Kentucky, Lexington, USA.
Delong
D
D
Clabots
C
C
Riciputi
P
P
Filice
G A
GA
D000818:Animals; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D004198:Disease Susceptibility; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000502:physiology*
D007371:Interferon-gamma