IL-12 deficiency transiently improves viral clearance during the late phase of respiratory tract infection with influenza A virus in mice

T helper 1-driven immune responses have been implicated in protective immunity against viral infections. Interleukin (IL)-12 is a heterodimeric proinflammatory cytokine formed by a p35 and a p40 Subunit that can induce differentiation of naive T cells towards a T helper 1-response. To determine the role of IL-12 in respiratory tract infection with influenza, p35 gene deficient (p35(-/-)) and normal wild type mice were intranasally infected with influenza A virus. IL-12 p35(-/-) mice displayed a transiently enhanced rather than an impaired viral clearance, as indicated by a 10-fold reduction in viral loads on day 8 after infection. Although interferon-gamma levels were significantly lower in the lungs of IL-12 p35(-/-) mice, their cellular immune responses were not altered, as reflected by similar T cell CD69 expression and influenza-specific T cell recruitment. Our data indicate that endogenous IL-12 impairs viral clearance during the late phase of influenza A virus infection in mice. (c) 2006 Elsevier B.V. All rights reserved.