Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration into the cornea

• Published in: Experimental eye research Vol. 86; no. 5; pp. 753 - 757
• Main Authors: Stapleton, W. Michael, Chaurasia, Shyam S., Medeiros, Fabricio W., Mohan, Rajiv R., Sinha, Sunilima, Wilson, Steven E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2008
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Bone Marrow Cells - pathology; Bone Marrow Cells - physiology; bone marrow-derived cells; CD11b Antigen - analysis; Cell Movement - drug effects; Cornea - drug effects; Cornea - pathology; Corneal Stroma - drug effects; Corneal Stroma - pathology; corneal wound healing; Disease Models, Animal; Drug Evaluation, Preclinical - methods; Epithelium, Corneal - drug effects; Epithelium, Corneal - injuries; Epithelium, Corneal - pathology; Female; Interleukin 1 Receptor Antagonist Protein - pharmacology; interleukin-1; keratocytes; Leukocyte Count; Mice; Mice, Inbred C57BL; monocytes; Monocytes - drug effects; Monocytes - pathology; Monocytes - physiology; Ophthalmic Solutions; receptor antagonist; Receptors, Interleukin-1 - physiology; Recombinant Proteins - pharmacology; Wound Healing - drug effects; corneal wound healing; monocytes; bone marrow-derived cells; interleukin-1; keratocytes; receptor antagonist
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2008.02.001

Interleukin (IL)-1α and β are important modulators of many functions of corneal epithelial and stromal cells that occur following injury to the cornea, including the influx of bone marrow-derived inflammatory cells into the stroma attracted by chemokines released from the stroma and epithelium. In this study, we examined the effect of topical soluble IL-1 receptor antagonist on bone marrow-derived cell influx following corneal epithelial scrape injury in a mouse model. C57BL/6 mice underwent corneal epithelial scrape followed by application of IL-1 receptor antagonist (Amgen, Thousand Oaks, CA) at a concentration of 20mg/ml or vehicle for 24h prior to immunocytochemical detection of marker CD11b-positive cells into the stroma. In two experiments, topical IL-1 receptor antagonist had a marked effect in blocking cell influx. For example, in experiment 1, topical IL-1 receptor antagonist markedly reduced detectible CD11b-positive cells into the corneal stroma at 24h after epithelial injury compared with the vehicle control (3.5±0.5 (standard error of the mean) cells/400× field and 13.9±1.2cells/400× field, respectively, p<0.01). A second experiment with a different observer performing cell counting had the same result. Thus, the data demonstrate conclusively that topical IL-1 receptor antagonist markedly down-regulates CD-11b-positive monocytic cell appearance in the corneal stroma. Topical IL-1 receptor antagonist could be an effective adjuvant for clinical treatment of corneal conditions in which unwanted inflammation has a role in the pathophysiology of the disorder.