Interleukin-8 levels and activity in delayed-healing human thermal wounds.
There are numerous causes for slow or delayed wound healing. Because slowly healing wounds are often inflamed, we quantitated the inflammatory chemokine, interleukin-8, produced by slowly healing human burn wounds and compared this to interleukin-8 from healed wounds and normal intact skin. Interleukin-8 levels were increased significantly in unhealed wounds (19.7 ng/ml) compared to healed wounds (7.7 ng/ml) or normal skin (5.7 ng/ml). Interleukin-8 in these ranges was added to adult human keratinocytes and fibroblasts. Interleukin-8 significantly decreased keratinocyte replication but had no effect on fibroblast replication. The rate or final degree of fibroblast populated collagen lattice contraction was inhibited at interleukin-8 concentrations between 10 and 30 ng/ml, but not altered at concentrations below 10 ng/ml and above 100 ng/ml. The concurrent application of indomethacin at 10 microg/ml reversed this interleukin-8 induced inhibition. Interleukin-8 inhibited myosin ATPase activity, apparently by reducing the phosphorylation of nonmuscle myosin light chain. We conclude that elevated levels of interleukin-8 may be found during delayed healing, and these elevated interleukin-8 levels may directly contribute to retarded wound closure.
Iocono
J A
JA
Division of Pediatric Surgery,Hershey Medical Center, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Colleran
K R
KR
Remick
D G
DG
Gillespie
B W
BW
Ehrlich
H P
HP
Garner
W L
WL
D000328:Adult; D002056:Burns / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D000078404:Epidermal Cells; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016209:Interleukin-8 / Q000032:analysis*; D015603:Keratinocytes; D018994:Myosin Light Chains; D010766:Phosphorylation; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*
D016209:Interleukin-8; D018994:Myosin Light Chains; D007213:Indomethacin