Published online before print May 22, 2003

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(Journal of Leukocyte Biology. 2003;73:713-721.)
© 2003 by Society for Leukocyte Biology

Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice

Zi-Qing Lin^*,, Toshikazu Kondo^*, Yuko Ishida^*, Tatsunori Takayasu^* and Naofumi Mukaida

Faculty of Forensic Medicine, China Criminal Police College, Shenyang, China; and
^* Department of Forensic & Social Environmental Medicine, Graduate School of Medical Science, and
Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Japan

Correspondence: Naofumi Mukaida, M.D., Ph.D., Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, 920-0934 Kanazawa, Japan. E-mail: naofumim{at}kenroku.kanazawa-u.ac.jp

To clarify interleukin (IL)-6 roles in wound healing, we prepared skin excisions in wild-type (WT) and IL-6-deficient BALB/c [knockout (KO)] mice. In WT mice, the wound area was reduced to 50% of original size at 6 days after injury. Microscopically, leukocyte infiltration was evident at wound sites. Furthermore, the re-epithelialization rate was 80% at 6 days after injury with increases in angiogenesis and hydroxyproline contents. The gene expression of IL-1, chemokines, adhesion molecules, transforming growth factor-ß1, and vascular endothelial growth factor was enhanced at the wound sites. In contrast, the enhanced expression of these genes was significantly reduced in KO mice. Moreover, in KO mice, the reduction of wound area was delayed with attenuated leukocyte infiltration, re-epithelialization, angiogenesis, and collagen accumulation. Finally, the administration of a neutralizing anti-IL-6 monoclonal antibody significantly delayed wound closure in WT mice. These observations suggest that IL-6 has crucial roles in wound healing, probably by regulating leukocyte infiltration, angiogenesis, and collagen accumulation.

Key Words: leukocyte recruitment • angiogenesis • collagen production • chemokines • TGF-ß1 • VEGF

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