title: Cadexomer as well as cadexomer iodine induces the production of proinflammatory cytokines and vascular endothelial growth factor by human macrophages.
abstract: Although cadexomer iodine is widely used for the treatment of skin ulcers such as decubitus ulcers, the mechanism by which it enhances wound healing is not clear. Recently, it has been demonstrated that macrophages play an important role in wound healing by inducing inflammation and angiogenesis. We examined the effects of cadexomer and cadexomer iodine on tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, IL-12 p 40, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) production by macrophages. Human macrophages were obtained by culturing CD14+ monocytes with macrophage colony stimulating factor (M-CSF) in the presence or absence of cadexomer or cadexomer iodine. The production of cytokines and the expression of mRNA were evaluated by enzyme linked immunosorbent assay (ELISA) of the culture supernatants and by reverse transcriptase polymerase chain reaction (RT-PCR) analysis, respectively. In addition, we examined the tissue concentration of VEGF in the wounds treated with or without cadexomer iodine. Cadexomer and cadexomer iodine significantly increased the expression of IL-1 beta, IL-8, TNF-alpha and VEGF mRNA, while they did not affect that of IL-6, IL-10, IL-12 p 40 or bFGF mRNA. In addition, they significantly increased the production of IL-1 beta and TNF-alpha. Although we could not detect increased production of VEGF in the culture supernatants, the western blot analysis of macrophages demonstrated the increased production of VEGF by the treatment with either cadexomer or cadexomer iodine. The treatment with cadexomer iodine increased the tissue concentration of VEGF in the skin wounds. These data suggest that cadexomer and cadexomer iodine have beneficial effects on wound healing in addition to those related to their antibacterial activity.
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohtani
authors.forename: Masato
authors.initials: M
authors.lastname: Mizuashi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017613:Iodine Compounds / Q000494:pharmacology*; D007466:Iodophors; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012883:Skin Ulcer / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016207:Cytokines; D017613:Iodine Compounds; D007466:Iodophors; D018950:Lipopolysaccharide Receptors; D016173:Macrophage Colony-Stimulating Factor; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C038634:cadexomer iodine