REGULATION OF INTERLEUKIN-6 EXPRESSION IN PORCINE IMMUNE CELLS

Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immu ne response, acute-phase reaction, and hematopoiesis. As a first step in studying the actions of IL-6 in pigs, the regulation of IL-6 expres sion was examined in various swine cells, including a fibroblast cell line, peripheral blood mononuclear cells (PBMC), and alveolar macropha ges. IL-6 expression in transformed swine testicular (TST) fibroblasts was enhanced by TNF and IL-1 beta and to a lesser extent by poly(I).( C) and LPS. IL-6 was induced in porcine PBMC by either LPS or PHA; how ever, the combination of LPS plus PHA resulted in maximal IL-6 express ion. Furthermore, in PBMC cells separated by adherence, LPS was a more potent inducer than PHA in adherent cells, whereas PHA was more poten t in nonadherent cells. Alveolar macrophages collected from different pigs could be divided into low and high responders with respect to IL- 6 induction by LPS. IL-6 mRNA induction by LPS could be detected in on ly 6 of 20 donor animals. Other inflammatory cytokines (IL-8, IL-1 bet a, and TNF) were readily induced by LPS in alveolar macrophages from b oth low and high responders. Treatment of low-responder alveolar macro phages with conditioned medium containing IFN-gamma did not significan tly alter the capacity of these macrophages to synthesize IL-6 mRNA in response to LPS. Comparison of IL-6 production capacity by the cell t ypes in this study revealed the following order: PBMC high-responder a lveolar macrophages >> TST cells > low-responder alveolar macrophages. Thus, PBMC appear to be quantitatively the most significant source of IL-6 in swine on a per cell basis.