Resolution of immune response by recombinant transforming growth factor-beta (rTGF-β) during influenza A virus infection

BACKGROUND & OBJECTIVES: Replication of influenza A virus in the respiratory tract leads to cell damage and liberation of cytokines and chemokines. The in vivo cytokine induction and modulation by recombinant transforming growth factor- β1 (rTGF-β1) has not been studied. Therefore, in the present study the effect of rTGF-β1, a potent immunomodulatory cytokine which has anti-inflammatory properties and downregulates the release of inflammatory molecules, against influenza-virus infection in the airway of mice was investigated. METHODS: rTGF-β1 was administered intravenously to mice with concomitant intranasal infection of influenza A/Udorn/317/72 (H3N2) virus, and the survival rate, virus titre, histopathological changes and levels of factors regulating inflammation in the airway fluid were analysed. RESULT: The immune response to influenza A virus was characterized by an influx of both macrophages and lymphocytes into the lungs of the infected host. rTGF-β1 significantly suppressed virus multiplication and improved the survival rate of mice. rTGF-β1 downregulated infiltration of neutrophils and the release of inflammatory molecules, such as interferon-gamma (IFN-γ), interleukin-1 β (IL-1β) and stimulated release of IL-10 that potentiates anti-inflammatory response into airway. INTERPRETATION & CONCLUSIONS: A generalized pulmonary inflammation does not contribute to viral clearance but represents an immunological background within which antiviral immunity operates. Treatment with rTGF-β1 reduced macrophage count and neutrophils influx in lungs of infected mice.