Interleukin-10 (IL-10) is an important anti-inflammatory molecule that can cause immunosuppression and long-term pathogen persistence during chronic infection of mice with viruses such as lymphocytic choriomeningitis virus. However, its specific role in immunity to acute viral infections is not fully understood. We found that IL-10 plays a detrimental role in host responses to acute influenza A virus since IL-10 ؊/؊ mice had improved viral clearance and survival after infection compared to wild-type mice. Enhanced viral clearance in IL-10 ؊/؊ mice was not correlated with increased CD4 ؉ or CD8 ؉ T-cell recruitment into the lung but was correlated with increased pulmonary anti-influenza virus antibody titers, and this was dependent upon the presence of T cells, primarily CD4 ؉ T cells. In addition, virus-specific antibody produced during the early stages of infection in the respiratory tract of IL-10 ؊/؊ but not wild-type mice was sufficient to mediate passive protection against viral challenge of naïve mice. Complement was necessary for this antibody-mediated passive protection, but Fc␥R or neutrophil deficiency did not significantly influence viral clearance. Our results show that an absence of IL-10 at the time of primary infection leads to enhanced local virus-specific antibody production and, thus, increased protection against influenza A virus infection.

IL‐10 is an important anti‐inflammatory molecule that can cause immunosuppression, leading to long‐term viral persistence during chronic infection of mice with viruses such as lymphocytic choriomeningitis virus. However, its specific role during acute viral infections has not been documented. We now report that IL‐10 appears to also play a detrimental role during host responses to acute influenza virus infection since absence of IL‐10 led to improved viral clearance, weight recovery and survival rate in influenza‐infected mice. There were similar levels of CD4+ and CD8+ T cell recruitment into the lungs of infected WT and IL‐10−/− mice, and depletion of CD8+ T cells did not significantly influence viral clearance in IL‐10−/− mice. Although viral infected IL‐10−/− mice exhibited different kinetics of neutrophil recruitment compared to WT mice, neutrophil depletion did not hamper viral clearance. On the other hand, H1N1‐specific antibody levels in BALF were slightly increased in viral infected IL‐10−/− mice compared to WT mice. The mechanism of IL‐10 mediated suppression of host recovery from influenza virus infection is under further investigation. (Supported by NIH grant RO1 AI 41715)