Impaired cutaneous wound healing in interleukin-6-deficient and immunosuppressed mice

It has been postulated that an inflammatory response after cutaneous woundi ng is a prerequisite for healing, and inflammatory cytokines, such as inter leukin-6 (IL-6), might be intimately involved in this process. IL-6-deficie nt transgenic mice (IL-6 KO) displayed significantly delayed cutaneous woun d healing compared with wild-type control animals, requiring up to threefol d longer to heal. This was characterized by minimal epithelial bridge forma tion, decreased inflammation, and granulation tissue formation. Using elect rophoretic mobility shift assays of wound tissue from IL-6 KO mice, decreas ed AP-1 transcription factor activation was shown compared with wild-type m ice 16 h after wounding. lit situ hybridization of wound tissue from wild-t ype mice revealed IL-6 mRNA expression primarily in the epidermis at the le ading edge of the wound. Delayed wound healing in IL-6 KO mice was reversed with a single dose of recombinant murine IL-6 or intradermal injection of an expression plasmid containing the full-length murine IL-6 cDNA. Treatmen t with rmIL-6 also reconstituted wound healing in dexamethasone-treated imm unosuppressed mice. The results of this study may indicate a potential use for IL-6 therapeutically where cutaneous wound healing is impaired.