Suppressive Effects of Transforming Factor-β and Interleukin-10 on the Cytolytic Activity of Murine Macrophages and Reversal by Cytokines
In this study, the suppressive effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on peritoneal macrophage killing of H238 target cells and the potential for reversal of the immunosuppressive effect by IL-4 and interferon-γ (IFN-γ) were investigated. The responsiveness of naive and peptone-activated macrophages was compared. The cytolytic activity for tumor cells of these effector cells was measured by percent lysis of 3H-thymidine labeled Herpes simplex virus type 2-transformed tumor cells (H238). After 18-24 hours of incubation with TGF-β or IL-10, the cytolytic activity of macro-medium alone. The immunosuppressive effect of TGF-β or IL-10 on non-activated macrophages was dose-dependent, with as little as 1 ng/ml TGF-β or 25.0 ng/ml IL-10, suppressing the cytolytic activity. After coincubation with TGF-β (5ng/ml) and IL-4 (200ng/ml) or IFN-γ (400 unit/ml), inhibition in the killing activity of macrophages was reversed by 20-30% when compared to controls incubated with TGF-β alone. IL-4 and IFN-γ both partially reversed the immunosuppressive effects of TGF-β on macrophages. When 10% proteose peptone was injected into mice to activate macrophages, the findings show that TGF-β could suppress non-activated macrophage cytotoxicity, but did not inhibit the cytotoxicity of peptone-activated cells. The killing activity of resting macrophages was significantly inhibited by 50 ng/ml of IL-10. When H238 tumor-bearing mice were treated with anti-TGF-β antibody (Ab), the results show that the production of tumor necrosis factor-α (TNF-α), a cytokine known to directly destroy tumors, in H238 tumor-bearing mice without treatment is lower than in H238 tumor-bearing mice with anti-TGF-β Ab treatment.
Animal Experimentation and Research, Immune System Diseases, Immunopathology, Immunotherapy, Laboratory and Basic Science Research, Microbiology, Oncology, Virus Diseases, Transforming Growth Factor beta; Interleukin-10; Macrophages; Cytokines; Immunosuppression
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