EFFECT OF CYTOKINES IN HOST DEFENSE AND INFLAMMATION

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Accumulation of neutrophils to sites of infection and inflammation is essential to host defense. When too few neutrophils accumulate there is increased susceptibility to infection. When too many neutrophils accumulate there can be tissue destruction. In recent years cytokines, products of numerous types of cells, have been shown to attract neutrophils to inflammation. One of these cytokines, IL-8 is critical for mobilizing normal numbers of neutrophils to inflammatory sites. This past year our investigations of the synthesis of IL-8, a potent chemoattractant, by neutrophils were continued. Previously we demonstrated that when human blood neutrophil s migrate into tissues they are induced to make abundant amounts of IL-8. In fiscal year '97 we utilized peripheral blood normal neutrophils from human subjects and we studied calcium metabolism and IL-8 synthesis and release. Our studies demonstrated two pathways for neutrophil IL-8 synthesis, one calcium dependent and the other calcium independent.