Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration into the cornea.
Interleukin (IL)-1alpha and beta 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 20 mg/ml or vehicle for 24 h 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/400x field and 13.9+/-1.2 cells/400x 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.
Stapleton
W Michael
WM
Cole Eye Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Chaurasia
Shyam S
SS
Medeiros
Fabricio W
FW
Mohan
Rajiv R
RR
Sinha
Sunilima
S
Wilson
Steven E
SE
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000473:pathology / Q000502:physiology; D039481:CD11b Antigen / Q000032:analysis; D002465:Cell Movement / Q000187:drug effects; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D003319:Corneal Stroma / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019573:Epithelium, Corneal / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009883:Ophthalmic Solutions; D017472:Receptors, Interleukin-1 / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; D053590:Interleukin 1 Receptor Antagonist Protein; D009883:Ophthalmic Solutions; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins