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(Investigative Ophthalmology and Visual Science. 2003;44:4412-4418.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.03-0246
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Effect of Human Cationic Antimicrobial Protein 18 Peptide on Endotoxin-Induced Uveitis in Rats

Kazuhiro Ohgami,1 Iliyana Bozhidarova Ilieva,1 Kenji Shiratori,1 Emiko Isogai,2 Kazuhiko Yoshida,1 Satoshi Kotake,1 Tomomi Nishida,3 Nobuhisa Mizuki,3 and Shigeaki Ohno3

1From the Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Sapporo, Japan; 2Department of Preventive Dentistry, Health Sciences University of Hokkaido, Hokkaido, Japan; and 3Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Japan.

PURPOSE. Human cationic antimicrobial protein 18 (hCAP18, 18 kDa) was originally identified in leukocytes on the basis of its antimicrobial activity. The peptide composed of the 27 C-terminal amino acids of hCAP18 (hCAP18109–135) binds lipopolysaccharide (LPS). The purpose of the present study was to investigate the effects of hCAP18 peptide on endotoxin-induced uveitis (EIU) in rats.

METHODS. EIU was induced by footpad injection of LPS. Each rat was injected intravenously with 1, 10, or 100 µg hCAP18 peptide in 0.1 mL of PBS immediately after LPS injection in male Lewis rats. At 24 hours after LPS injection, enzyme-linked immunosorbent assay was performed to evaluate concentrations of protein, nitric oxide (NO), tumor necrosis factor (TNF)-{alpha}, prostaglandin (PG)-E2, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 in aqueous humor. Also, EIU was evaluated by counting inflammatory cells in aqueous humor.

RESULTS. hCAP18 peptide at 10 and 100 µg significantly suppressed an LPS-induced increase in the number of inflammatory cells and the levels of protein, NO, TNF-{alpha}, PGE2, MCP-1, and MIP-2. The anti-inflammatory effect of 10 µg hCAP18 peptide was as strong as that of 100 µg hCAP18 peptide. Treatment with 1 µg hCAP18 peptide did not suppress EIU, compared with the LPS group.

CONCLUSIONS. The present results indicate that hCAP18 peptide suppresses development of EIU. A possible mechanism for the ocular anti-inflammatory effect of hCAP18 peptide is that it suppresses onset of LPS-triggered inflammatory reactions by binding directly to LPS.




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