Bronchoalveolar Interferon-α, Tumor Necrosis Factor-α, Interleukin-1, and Inflammation during Acute Influenza in Pigs: A Possible Model for Humans?

Van Reeth, Kristien; Nauwynck, Hans; Pensaert, Maurice

Biologically active interferon-α, tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1 influenza virus. Cytokine titers and lung virus titers were significantly higher 18–24 h after inoculation than at 48–72 h after inoculation in all 4 litters of pigs examined. All three cytokines were positively correlated with a 3- to 4-fold increase in BAL cell numbers (P < .036) and with a drastic neutrophil infiltration (24%–77% of BAL cells vs. 0–1.5% in controls) (P < .001). In addition, cytokine production coincided with the onset of general and respiratory symptoms of influenza and with the development of a necrotizing bronchopneumonia. This study is the first demonstration of TNF-α and IL-1 in BAL fluids of a natural influenza virus host. It documents that pigs may be a highly valuable experimental model in human influenza virus pneumonia.