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Z. Sadrai, A. R. Hajrasouliha, S. K. Chauhan, D. R. Saban, M. H. Dastjerdi, R. Dana; Effect of Topical Azithromycin on Innate Immune Responses in Experimental Keratitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5536.
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Azithromycin (AZM) is a broad-spectrum macrolide antibiotic which may have endogenous anti-inflammatory properties similar to other macrolides via suppression of NF-kB signal transduction pathway. This study aimed to determine the potential immunomodulatory effects of AZM on corneal inflammation.
6-8 week old BALB/c mice underwent thermal cautery to the corneal surface to induce inflammation and leukocyte influx. Corneas were treated topically either with AZM ophthalmic solution 1% (AzaSite®; Inspire Pharmaceuticals, Inc, NC, USA) or the relevant vehicle, twice per day. Corneas were harvested at various time-points (day 1, 3, 7, 10, and 14) to characterize the inflammatory infiltrates via FACS analysis, and to quantitate relevant chemokines/cytokines via real time PCR.
AZM treatment significantly decreased the overall influx of total bone marrow-derived (CD45+) cells on day 7 by nearly 40%. The majority of the reduction in the CD45+ cells appeared to be found among the CD11b+ (macrophage) and CD11c+ (dendritic cell) subsets, but not among Gr-1+ cells (neutrophils). Moreover, pro-inflammatory chemokines CXCL10 and CCL5, and IL-1beta levels were significantly reduced (p<0.05) on day 7 with AZM treatment.
Topical AZM reduces infiltration of macrophages and dendritic cells considerably in inflamed corneas. This was further supported by an associated reduction in CXCL10 and CCL5, as well as IL-1beta. In addition to its anti-microbial properties, topical AZM holds anti-inflammatory properties in a mouse model of keratitis.
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