Effects of IFN-α on the Inflammatory Response of Swine Leukocytes to Bacterial Endotoxin

Abstract

Because low-dose interferon-α (IFN-α) treatment had proved effective in several models of chronic inflammation and autoimmune disease, a possible role of IFN-α in modulating the response of swine leukocytes to bacterial endotoxin was investigated in this study. Exposure of swine peripheral blood mononuclear cells(PBMC) to low concentrations of human IFN-α caused a strong, dose-dependent decrease in CD14 expression, the lowest level being observed at 5 U/ml IFN-α. This result was confirmed if PBMC were later exposed to purified lipopolysaccharide (LPS). A 10-fold lower IFN-α concentration (0.5 U/ml) caused the largest reduction of tumor necrosis factor-α (TNF-α) accumulation in the medium of pulmonary alveolar macrophages(PAM), stimulated with bacterial LPS. At 0.5 U/ml, the expression of the TNF-α gene in PAM was also strongly reduced, as opposed to cells pretreated with 50 U/ml IFN-α. In contrast, expression of the interleukin-1β (IL- 1β) gene was stimulated and that of the IL-6 gene was not significantly affected at both IFN-α concentrations. Results point to an important role of IFN-α in control of the inflammatory response to bacterial endotoxin in pigs.