Interleukin-6 (IL-6) is a multifunctional cytokine with local and systemic effects during immunological and inflammatory reactions. The IL-6 activity in wound fluids and serum from wounded animals, its release by wound cells in culture, and its role in the regulation of wound fibroblast proliferation were determined. IL-6 activity in wound fluid and serum peaked within 12 h after wounding. Wound-derived polymorphonuclear leukocytes, macrophages, and fibroblasts released IL-6 in culture. Wound macrophages harvested 5 days after injury produced more IL-6 than those taken at 3 or 10 days. An anti-IL-6 antibody partially reversed the suppression of wound fibroblast proliferation by wound fluid and wound macrophage culture supernatants. Finally, human wound fluids exhibited a temporal pattern of IL-6 activity similar to that found in rat wounds. The early wound, then, and more specifically the polymorphonuclear leukocytes of the immediate inflammatory response appear to be the source of circulating IL-6 after injury. In the later wound, IL-6 may provide signals to suppress fibroblast proliferation.
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