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

Abstract

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 marrowderived 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 24 h after epithelial injury compared with the vehicle control (3.5 ± 0.5 (standard error of the mean) cells/400× field and 13.9 ± 1.2 cells/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.

Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas

“…17,18 Interestingly, topical application of IL-1Ra was shown to inhibit inflammatory cell infiltration into the cornea, but its effect on epithelial wound closure was not reported. 19 In the skin, IL-1Ra has been implicated in skin wound healing and fibrosis, with evidence of reduced skin fibrosis after application of anakinra, human recombinant IL-1Ra. 20,21 The role(s) of IL-1 and IL-1Ra in reepithelialization, particularly their unbalanced production in DM tissues, remains elusive.…”

Wound Repair and Regeneration

“…PA treated mice showed significant NF-κB binding activity when compared to control group in both ear and back skin. On the contrary, 145 Books MDPI NF-κB binding activity in TECA treated mice was significantly inhibited when compared with PA treated mice ( Figures 3D and 4D). In addition, as shown in Figures 3E and 4E, PA treated mice showed significant IκBα degradation in cytosolic fraction when compared to the control group in both ear and back skin.…”

Important Role of Epiregulin in Inflammatory Responses during Corneal Epithelial Wound Healing

“…28 Topical application of IL-1 receptor antagonist inhibited inflammatory cells from infiltrating the cornea after epithelial injury. 26 IL-1 can also stimulate the production of other inflammatory mediators. Thus, Yang et al 29 reported that CXCL1, IL-6, and IL-8 (of the 36 molecules tested) were elevated after exposure to IL-1b in HeLa cells.…”

“…It is an important regulator of ocular surface inflammatory responses. [25][26][27] For example, after inhibiting the elevated IL-1b by anti-IL-1b antibody in Pseudomonas aeruginosa-induced ocular infections, the degree of corneal inflammation and rate of perforation were reduced by a reduction in the CXCL2 level and the number of PMN cells. 28 Topical application of IL-1 receptor antagonist inhibited inflammatory cells from infiltrating the cornea after epithelial injury.…”