Submitted to: Cytokine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/6/2010
Publication Date: 1/3/2011
Citation: He, H., Genovese, K.J., Kogut, M.H. 2011. Modulation of chicken macrophage effector function by Th1/Th2 cytokines. Cytokine. 53:363-369.
Interpretive Summary: Cytokines are chemicals that control and direct the immune response of white blood cells, such as the macrophage. We looked at the effects of the cytokines interferon-gamma and interleukin-4 on the production of chemicals macrophage used to kill bacteria and viruses. We found that interferon-gamma and interleukin-4 play very important and different roles in the activation of the chicken macrophage and in maintaining a balanced immunity. The data shows that these two important cytokines have differential activity on macrophage, with both cytokines providing protection against infection while interleukin-4 also simultaneously acts to prevent the adverse effects of inflammation. The data suggests that manipulation of cytokines may provide an alternative method of increasing the immune response in chickens to fend off infections such as Salmonella and other food-borne pathogens.
Technical Abstract: Regulation of macrophage activity by TH1/2 cytokines is important to maintain the balance of immunity to provide adequate protective immunity while avoiding excessive inflammation. IFN-gamma and IL-4 are the hallmark TH1 and TH2 cytokines, respectively. In avian species, information concerning regulation of macrophage activity by TH1/2 cytokines is limited. Here, we investigated the regulatory function of chicken TH1 cytokines IFN-gamma, IL-18 and TH2 cytokines IL-4, IL-10 on the HD11 macrophage cell line. Chicken IFN-gamma stimulated nitric oxide (NO) synthesis in HD11 cells and primed the cells to produce significantly greater amounts of NO when exposed to microbial agonists lipopolysaccharide, lipoteichoic acid, peptidoglycan, CpG-ODN, and poly I:C. In contrast, chicken IL-4 exhibited bi-directional immune regulatory activity: it activated macrophage NO synthesis in the absence of inflammatory agonists but inhibited NO production by macrophages in response to microbial agonists. Both IFN-gamma and IL-4, however, enhanced oxidative burst activity of the HD11 cells when exposed to Salmonella enteritidis. IL-18 and IL-10 did not affect NO production nor oxidative burst in HD11 cells. Phagocytosis and bacterial killing by the HD11 cells were not affected by the treatments of these cytokines. Infection of HD11 cells with S. enteritidis was shown to completely abolish NO production regardless of IFN-gamma treatment. This study has demonstrated that IFN-gamma and IL-4 are important TH1 and TH2 cytokines that regulate macrophage function in chickens.