title: Anti-inflammatory effect of IL-6 receptor blockade in corneal alkali burn.
abstract: We investigated the effect of soluble IL-6R (sIL-6R) blockade on corneal inflammation. Topical instillation of either anti-IL-6R antibody (MR16-1) or phosphate buffered saline (PBS) was applied after wounding BALB/c mice corneas with alkali burn. The vascularized area was significantly reduced in the MR16-1 group. The immunoreactivity of phosphorylated STAT3, Gr-1, and F4/80 diminished significantly in the MR16-1 group. Laser capture microdissection resulted in a significant down-regulation of the mRNA expressions of ICAM-1, MCP-1, and VEGF-A in the corneal stroma of the MR16-1 group. Adding a combination of recombinant IL-6 and sIL-6R resulted in a significant increase in the release of VEGF from human corneal fibroblasts. As the infiltration of inflammatory cells, the expression of phosphorylated STAT3, and the expressions of inflammatory-related molecules in the experimental model of corneal inflammation were significantly inhibited by topical instillation of MR16-1, we deduce that IL-6 trans-signaling plays a significant role in ocular surface inflammation and that the blockade of IL-6R contributes to the reduction in corneal inflammation.
authors.affiliation: Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, 30-1 Oyaguchi Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. torusaki@gmail.com
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sugaya
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishimori
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sawa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D002057:Burns, Chemical / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D060527:Corneal Keratocytes / Q000187:drug effects / Q000378:metabolism; D016510:Corneal Neovascularization / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D005126:Eye Burns / Q000139:chemically induced*; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology; D007634:Keratitis / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012972:Sodium Hydroxide; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C090509:Icam1 protein, mouse; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D018799:Intercellular Adhesion Molecule-1; D012972:Sodium Hydroxide