Effects of IFN-alpha on the inflammatory response of swine leukocytes to bacterial endotoxin.
Because low-dose interferon-alpha (IFN-alpha) treatment had proved effective in several models of chronic inflammation and autoimmune disease, a possible role of IFN-alpha 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-alpha caused a strong, dose-dependent decrease in CD14 expression, the lowest level being observed at 5 U/ml IFN-alpha. This result was confirmed if PBMC were later exposed to purified lipopolysaccharide (LPS). A 10-fold lower IFN-alpha concentration (0.5 U/ml) caused the largest reduction of tumor necrosis factor-alpha (TNF-alpha) accumulation in the medium of pulmonary alveolar macrophages (PAM), stimulated with bacterial LPS. At 0.5 U/ml, the expression of the TNF-alpha gene in PAM was also strongly reduced, as opposed to cells pretreated with 50 U/ml IFN-alpha. In contrast, expression of the interleukin-1beta (IL- 1beta) gene was stimulated and that of the IL-6 gene was not significantly affected at both IFN-alpha concentrations. Results point to an important role of IFN-alpha in control of the inflammatory response to bacterial endotoxin in pigs.
Begni
Barbara
B
Department of Immunoprophylaxis and Animal Welfare, Istituto Zooprofilattico Sperimentale, 25124 Brescia, Italy.
Amadori
Massimo
M
Ritelli
Marco
M
Podavini
Damiano
D
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D004731:Endotoxins / Q000494:pharmacology*; D015870:Gene Expression; D018836:Inflammation Mediators / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013552:Swine / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D004731:Endotoxins; D018836:Inflammation Mediators; D016898:Interferon-alpha; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C044101:endotoxin, Escherichia coli