Modulation of chicken macrophage effector function by TH1/TH2 cytokines

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-γ 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-γ, IL-18 and TH2 cytokines IL-4, IL-10 on the HD11 macrophage cell line. Chicken IFN-γ 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-γ and IL-4, however, enhanced oxidative burst activity of the HD11 cells when exposed to Salmonellaenteritidis. 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-γ treatment. This study has demonstrated that IFN-γ and IL-4 are important TH1 and TH2 cytokines that regulate macrophage function in chickens.