INTERLEUKIN-10 INHIBITS INTERLEUKIN-2-INDUCED TUMOR-NECROSIS-FACTOR PRODUCTION BUT DOES NOT REDUCE TOXICITY IN C3H HEN MICE/

Immunotherapy with interleukin-2 (IL-2) is limited by severe side effe cts thought to be mediated by the activation of immune effector cells and the induction of secondary cytokines including tumor necrosis fact or-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). In C3H/HeN mice the primary IL-2 toxicity is the production of pleural effusion with subsequent respiratory compromise, IL-10 is a cytokine that has been s hown to inhibit the generation of secondary cytokines in vitro and in vivo. In this study, in C3H/HeN mice, we tested the ability of IL-10 t o inhibit IL-2-induced mononuclear cell and alveolar macrophage activa tion and IL-2-induced increases in serum TNF-alpha and IFN-gamma, all of which may contribute to the generation of toxicity, IL-10 was ineff ective at reducing IL-2-induced pleural effusion, However, IL-10 did i nhibit 1L-2-induced increases in serum TNF-alpha, which was accompanie d by a decrease in Golgi apparatus and rough endoplasmic reticulum in alveolar macrophages. In addition, IL-10 combined with IL-2 increased mononuclear cell activation, which may limit the ability of IL-10 to i nhibit IL-2-induced IFN-gamma production and pulmonary injury.