NEUTROPHIL STIMULATION BY RECOMBINANT CYTOKINES AND A FACTOR PRODUCED BY IL-1-TREATED HUMAN SYNOVIAL CELL-CULTURES

  • 1 December 1988
    • journal article
    • research article
    • Vol. 65  (4) , 567-572
Abstract
Neutrophil acumulation and activation are early events in the inflammatory response in vivo. Using human recombinant forms of the putative inflammatory mediators interleukin-1 (IL-1) and tumour necrosis factor (TNF.alpha.) we were unable to detect direct effects on human neutrophil locomotion or intracellular free calcium concentration ([Ca2+]i) in vitro. Human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was able to stimulate significant locomotion, but was unable to elevate neutrophil [Ca2+]i. In contrast, supernatant from cultured human synovial cells that had been treated with human recombinant IL-1.alpha. (28 pM) released a factor that stimulated both neutrophil locomotion and elevated neutrophil [Ca2+]i. Our studies demonstrate that the production of this factor is time-dependent, requiring exposure of the synovial cells to IL-1 for more than 4 hr, is not influenced by cylco-oxygenase or lipo-oxygenase inhibition, but can be abolished by dexamethasone (100 nM) or actinomycin D (0.8 .mu.M). The factor has a molecular weight above 10,000 and does nor cross-react with anti-C5a antisera. IL-1.beta. and TNF.alpha. were also able to stimulate its production. Our findings suggest that the neutrophil accumulation that is known to occur in response to IL-1 in vivo may be consequence of the local production of such a factor.

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