TIMP-1 Promotes the Immune Response in Influenza-Induced Acute Lung Injury.

INTRODUCTION: Influenza infects millions of people each year causing respiratory distress and death in severe cases. On average, 200,000 people annually are hospitalized in the United States for influenza related complications. Tissue inhibitor of metalloproteinase-1 (TIMP-1), a secreted protein that inhibits MMPs, has been found to be involved in lung inflammation. Here, we evaluated the role of TIMP-1 in the host response to influenza-induced lung injury.

METHODS: Wild-type (WT) and Timp1-deficient (Timp1-/- ) mice that were 8-12 weeks old were administered A/PR/8/34 (PR8), a murine adapted H1N1 influenza virus, and euthanized 6 days after influenza installation. Bronchoalveolar lavage fluid and lungs were harvested from each mouse for ELISA, protein assay, PCR, and histological analysis. Cytospins were executed on bronchoalveolar lavage fluid to identify immune cells based on morphology and cell count.

RESULTS: WT mice experienced significantly more weight loss compared to Timp1-/- mice after influenza infection. WT mice demonstrated more immune cell infiltrate and airway inflammation. Interestingly, PR8 levels were identical between the WT and Timp1-/- mice 6 days post-influenza infection.

CONCLUSION: The data suggest that Timp1 promotes the immune response in the lungs after influenza infection facilitating an injurious phenotype as a result of influenza infection.