Interleukin 6 plays a critical role in cutaneous wound healing.
Gallucci-RM; Sugawara-T; Simeonova-PP; Matheson-JM; Kommineni-C; Guriel-GK; Berry-Ann-R; Luster-MI
FASEB J 2001 Mar; 15(4):A355
It has been postulated that an inflammatory response following cutaneous wounding is a prerequisite for healing, and inflammatory cytokines, such as interleukin 6 (lL-6), might intimately involved in this process. Herein, we demonstrate that IL6 deficient transgenic mice (lL-6 KO) displayed significantly delayed cutaneous wound healing compared to wild type control animals, requiring up to three fold longer to heal. This was characterized minimal epithelial bridge formation, decreased inflammation, and granulation tissue formation. Delayed wound healing in IL-6 KO mice was reversed with a single dose of recombinant murine IL6 or intradermal injection of an expression plasmid containing the full length murine IL6 cDNA. We also demonstrate that dexamethasone significantly delays wound healing characterized by delayed re-epithelialization, granulation tissue formation and wound closure. Healing in the dexamethasone treated mice also can be augmented by administration of rmIL-6. In situ hybridization of wound tissue from wild type mice revealed IL-6 mRNA expression primarily in the epidermis at the leading edge of the wound. To further delineate the role of IL-6 in epidermal regeneration, we demonstrate that IL-6 mRNA is expressed and immunoreactive IL-6 is released from normal human epidermal keratinocytes (NHEKs) following in vitro wounding. We also show that IL-1 receptor antagonist will block wound induced IL-6 induction, and that constitutive keratinocyte-derived IL-1 is a major stimulus for IL-6 production in wounded epidermis. These results indicate the importance of IL-6 in wound healing, and a possible therapeutic application of this cytokine.
Immune-reaction; Immune-system; Immunological-tests; Injuries; Animals; Animal-studies; Laboratory-animals
Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, 1095 Willowdale Road, Morgantown, WV 26505-2845
Abstract; Conference/Symposia Proceedings
The FASEB Journal. Experimental Biology 2001, Orlando, Florida, March 13 - April 4, 2001