Rennekampff HO, Hansbrough JF, Kiessig V, Doré C, Sticherling M, Schröder JM, et al.
The Journal of surgical research. Date of publication 2000 Sep 1;volume 93(1):41-54.
1. J Surg Res. 2000 Sep;93(1):41-54.
Bioactive interleukin-8 is expressed in wounds and enhances wound healing.
Rennekampff HO(1), Hansbrough JF, Kiessig V, Doré C, Sticherling M, Schröder JM.
Author information:
(1)Department of Surgery, University of California, San Diego, California 92103,
USA.
BACKGROUND: Wound healing is a sequential biological process that involves the
integration of chemotaxis of neutrophils, mitosis and migration of keratinocytes,
and remodeling of the scar, all of which are regulated by specific soluble
mediators. To modulate wound healing specific mediators have to be identified and
functionally characterized. Therefore we addressed this study on the
polymorphonuclear leukocyte (PMN) attractant interleukin-8 (IL-8) and its
function in epidermal wound healing.
MATERIALS AND METHODS: Peptide purification, bioassays for PMN chemotaxis, and
sequential IL-8 measurements were performed on human wound fluid from burn
blisters and skin graft donor sites. Histology for IL-8 immunoreactivity was
included. In vitro human keratinocytes were assayed for proliferation, migration,
and integrin expression after IL-8 treatment. Wounding experiments with topical
IL-8 were performed in a chimeric mouse model.
RESULTS: IL-8 was found to be the major bioactive chemoattractant for PMNs in
human blister and skin graft donor site wound fluids (mean levels ranging from
173 ng/ml Postoperative Day (POD) 1 to 2130 ng/ml (POD 5)). Released
intracellular epidermal IL-8 immunoreactivity at the wound edge was considered as
an immediate source of IL-8 while NH(2)-terminal analysis revealed the
77-amino-acid residue form as a second source of IL-8 possibly PMN derived. In
vitro experiments on the effect of recombinant human (rh) IL-8 on keratinocyte
proliferation revealed a rise in cell number (4.8-fold, ED(50) = 0.6 ng/ml),
which was accompanied by an increase in cells in S phase and overexpression of
the integrin subunit alpha6. In vivo topically applied IL-8 (1 microg/ml) on
human skin grafts in a chimeric mouse model enhanced reepithelialization in IL-8
treated animals over controls due to elevated numbers of mitotic keratinocytes.
Wound contraction was significantly diminished by topical IL-8.
CONCLUSIONS: These results indicate the sequential function of endogenous IL-8 in
all phases of human wound healing. Topical IL-8 may be useful in impaired wound
healing.
Copyright 2000 Academic Press.
DOI: 10.1006/jsre.2000.5892
PMID: 10945942 [Indexed for MEDLINE]
