Interleukin-6 treatment augments cutaneous wound healing in immunosuppressed mice.
It has been postulated that the inflammatory response that occurs after cutaneous wounding is a prerequisite for healing and that inflammatory cytokines, such as interleukin-6 (IL-6) are involved in this process. We showed previously that IL-6-deficient mice display delayed wound healing, which could be reversed by administration of a murine IL-6 expression plasmid or recombinant murine IL-6 (rMuIL-6). In the present study, we observed that delayed cutaneous wound healing, which occurs as a result of glucocorticoid-induced immunosuppression, can also be reversed by rMuIL-6, as evidenced by epithelialization, granulation tissue formation, and wound closure. In vehicle control mice, rMuIL-6 did not augment healing but rather delayed the process. Immunochemical studies indicated that the expression of matrix metalloproteinase-10 (MMP-10) was increased in dexamethasone-treated mice and that rMuIL-6 treatment reduced its expression, indicating that IL-6 may influence dermal matrix formation and, specifically, collagen synthesis. These results demonstrate that IL-6 can restore abnormal wound repair that occurs in immunodeficiency and suggest its use as a potential therapy.
Gallucci
R M
RM
Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, NIOSH/CDCP, 1095 Willowdale Road, Morgantown, WV 26505-2888, USA.
Sugawara
T
T
Yucesoy
B
B
Berryann
K
K
Simeonova
P P
PP
Matheson
J M
JM
Luster
M I
MI
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003907:Dexamethasone / Q000008:administration & dosage / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000008:administration & dosage*; D008297:Male; D053506:Matrix Metalloproteinase 10; D008666:Metalloendopeptidases / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D003907:Dexamethasone; D008666:Metalloendopeptidases; D053506:Matrix Metalloproteinase 10