EFFECT OF CYTOKINES IN HOST DEFENSE AND INFLAMMATION

点击翻译按钮获取中文摘要

Studies have been initiated to explore the importance of cytokines in phagocyte function. Studies of phagocytes from patients with AIDS who were receiving interferon gamma or interleukin-2 indicated that patients receiving interferon gamma had markedly fewer bacterial infections than those receiving interleukin-2. We also studied the effect of interferon gamma on neutrophils and monocytes from patients with chronic granulomatous diseases of childhood (CGD). Interferon gamma corrected the abnormal oxidative metabolism in the phagocytes of many CGD patients in vitro and in vivo the drug was shown to reconstitute the defect as well. On other studies the effect of interferon gamma in the Hyperimmunoglobulin E and Recurrent Infections (Job's) Syndrome indicate that in vitro and in vivo interferon gamma down regulates B cell synthesis of IgE while in vivo interferon gamma lowers the elevated IgE in this syndrome towards normal. Interferon gamma was shown to cause monocyte polykaryon formation, in an in vitro model of granuloma formation, through a cascade of events involving interleukin-l and tumor necrosis factor. The latter effects could be blocked in vitro by use of corticosteroids. In other studies of the growth of mononuclear phagocytes, a technique was determined for developing human macrophage cell lines without transformation. Studies of the effect of interferon gamma on monocyte polykaryon formation demonstrated that human macrophages produce copious amounts of CSF-l and this may relate to an additional observation that under appropriate conditions human monocyte replication occurs in vitro when using "conditioned" growth media, rich in CSF-l.