BRONCHOALVEOLAR INTERFERON-ALPHA, TUMOR-NECROSIS-FACTOR-ALPHA, INTERLEUKIN-1, AND INFLAMMATION DURING ACUTE INFLUENZA IN PIGS - A POSSIBLE MODEL FOR HUMANS

Biologically active interferon-alpha, tumor necrosis factor-alpha (TNF -alpha), and interleukin-1 (IL-1) were detected in bronchoalveolar lav age (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pig s 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 c ytokines were positively correlated with a 3- to 4-fold increase in BA L 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 respirator y symptoms of influenza and with the development of a necrotizing bron chopneumonia. This study is the first demonstration of TNF-alpha and I L-1 in BAL fluids of a natural influenza virus host. It documents that pigs may be a highly valuable experimental model in human influenza v irus pneumonia.