Submitted to: Cellular Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/3/1997
Publication Date: N/A
Interpretive Summary: Mononuclear phagocytes (Mps) are members of the white blood cells that function in immune responses. This group of cells act as 1) processing sites for infectious disease organisms, 2) effector cells to kill the organisms and 3) regulatory cells providing a level of control over themselves and other groups of white blood cells. Regulation is important in orchestrating the correct immune response at the appropriate time. This occurs through products called cytokines produced by the cells that interact with other cells stimulating them to function as they are programmed to do. Our study identified a cytokine (IL-10) associated with Mps from cattle that appears to control the production of other cytokines from other cells, and other products from Mps themselves. The evidence suggests that these cells and IL-10 are important in limiting the immune response. This information will help in defining the correct response against the disease agents of interest to our research focus.
Technical Abstract: We previously demonstrated that iNOS can be induced in cultured bovine monocytes in response to IFN-gamma and TNF-alpha, but lose this capability in a short period of time. However, in this study we demonstrate that monocytes cultured with gamma deltaT-cells show prolonged nitric oxide production compared to monocyte cultures devoid of these cells, suggesting that gamma deltaT- cells may be a source of IFN-gamma to prime the monocytes before exogenous stimulation. Based on mRNA expression, placement of monocytes in culture resulted in activation, followed by quiescence. By 6 days in culture, iNOS message was reduced below the basal level. In addition, TNF-alpha was somewhat reduced, and IL-1, and IL-6, were reduced below detectable levels. This correlated with an increase in IL-10 message. Further, down regulation of these cytokine messages as well as IFN-gamma message occurred within a 20 hour period when IL-10 was added exogenously to cultures of total leukocytes. At the same time, there was an increase in both the intensity of anti-IL-10 staining within adherent cells as well as an increase in the number of IL-10-positive cells. The results provide evidence for IL-10 regulation of some mononuclear phagocyte effector functions.