Abstract
Influenza causes 3-5 million severe cases globally each year, with severe viral pneumonia often requiring hospitalization for over four weeks. While the inflammatory response to influenza infection helps control viral replication, excessive inflammation is a key driver of disease severity and mortality. Excessive pulmonary lymphocytes, particularly IFN-γ-producing T lymphocytes, contribute significantly to pulmonary inflammation at the late-stage of H1N1 viral infection. Cyclosporin A, a potent T-cell inhibitor, mitigates influenza A virus-induced pulmonary inflammation in mice. However, the therapeutic role of lymphocyte suppression in cyclosporin A-mediated attenuation of H1N1 virus-induced chronic pulmonary inflammation remains unclear. Here, we demonstrated that the viral titer was 0 in all the homogenized lung tissues of mice on Day-21 post a sublethal H1N1 viral infection. H1N1 viral infection caused worsened general condition and pulmonary inflammation with the infiltration of lymphocytes and neutrophils on Day-21 post-infection. The bronchoalveolar lavage fluid of H1N1 virus-infected mice showed a 16-fold higher lymphocyte count compared to neutrophils. H1N1 viral infection significantly elevated both IFN-γ-producing T lymphocyte populations and IFN-γ levels in mouse lungs. H1N1 viral infection additionally expanded IFN-γ-producing T lymphocyte populations in both spleen and peripheral blood. Cyclosporin A treatment significantly mitigated H1N1 viral infection-induced worsened general condition, pulmonary lymphocytic inflammation, increases of pulmonary IFN-γ concentrations and IFN-γ-producing T lymphocytes in the lung, spleen and blood of mice on Day-21 post-infection. Together, lymphocytes may contribute significantly to H1N1 virus-induced chronic pulmonary inflammation. Cyclosporin A may alleviate H1N1 virus-induced chronic pulmonary inflammation through decreasing IFN-γ-producing T lymphocytes.