Regulation of Interleukin-6 Expression in Porcine Immune Cells

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune response, acute-phase reaction, and hematopoiesis. As a first step in studying the actions of IL-6 in pigs, the regulation of IL-6 expression was examined in various swine cells, including a fibroblast cell line, peripheral blood mononuclear cells (PBMC), and alveolar macrophages. 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; however, the combination of LPS plus PHA resulted in maximal IL-6 expression. Furthermore, in PBMC cells separated by adherence, LPS was a more potent inducer than PHA in adherent cells, whereas PHA was more potent 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 only 6 of 20 donor animals. Other inflammatory cytokines (IL-8, IL-beta, and TNF) were readily induced by LPS in alveolar macrophages from both low and high responders. Treatment of low-responder alveolar macrophages with conditioned medium containing IFN-gamma did not significantly alter the capacity of these macrophages to synthesize IL-6 mRNA in response to LPS. Comparison of IL-6 production capacity by the cell types in this study revealed the following order: PBMC = high-responder alveolar 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.

Effects of particulate debris on macrophage-dependent fibroblast stimulation in coculture

“…19 Such factors may act alone, by interactions with other mediators, or through escalation of receptors to stimulate fibroblasts to increased release of IL-6. 18,20,21 The increase in IL-6 during interaction of macrophages and fibroblasts may be important in periprosthetic membranes in vivo, in which the high IL-6 level may contribute to accelerated bone resorption due to the stimulation of osteoclasts. 22,23 This interaction may be more important to inflammation and subsequent bone resorption in periprosthetic tissue than the cytokine release occurring from macrophages after phagocytosis and activation by wear particles.…”

Effects of DNA dose, route of vaccination, and coadministration of porcine interleukin-6 DNA on results of DNA vaccination against influenza virus infection in pigs

“…Bioactivity of pIL-6 in the transfected MDCK cell supernatants was determined by use of the B9 cell assay, as described. 50 Bioactive pIL-6 was quantified by comparison with a standard curve constructed by use of recombinant human IL-6. d To ensure that the activity detected in this assay was caused by IL-6, additional B9 cells were pretreated with monoclonal antibody (Mab) 15A7 against the gp130 subunit of the IL-6 receptor e (500 ng Mab/well of a 96-well plate for 2 hours at 37 C).…”

Lymphocyte Apoptosis and Thrombocytopenia in Spleen during Classical Swine Fever: Role of Macrophages and Cytokines

“…The major cytokines secreted by these cells include tumor necrosis factor α (TNF-α), which causes tissue necrosis and prompts death by apoptosis, 1, 55 and IL-1, which displays chemotactic activity 54 and is also involved in the induction of apoptosis. 38, 40 These two cytokines trigger production of the major pyrogenic cytokine IL-6, 43 which is involved both in the hepatocyte production of acute-phase proteins and in the regulation and differentiation of several cell types. 2 These cytokines appear to be associated with increased vascular permeability, and reports suggest that they are partly responsible for the hemorrhaging characteristic of human viral diseases.…”