Role and regulation of CXC-chemokines in acute experimental keratitis

The aim of this study was to elucidate the expression of chemokines, their role and regulation in bacterial corneal infection using three bacterial strains (Pseudomonas. aeruginosa- invasive, cytotoxic and contact lens induced acute red eye strains) which have been shown to produce three distinct patterns of corneal disease in the mouse. The predominant chemokine expressed in response to all three strains was MIP-2. Prolonged expression of high levels of MIP-2 was associated with increased severity of corneal inflammation. Significantly reduced disease severity upon administration of anti-MIP-2 antibodies suggested that MIP-2 may play an important role in the pathogenesis of Pseudomonas keratitis at least in part by being a major chemoattractant for polymorphonuclear leukocytes (PMN) recruitment. Interestingly, the numbers of bacteria in eyes with neutralized MIP-2 activity did not decrease even though the severity of the disease was decreased. This implies PMNs as the major destructive factor in microbial keratitis. Further, neutralization of IL-1beta activity alone using monoclonal antibodies resulted in significant reduction of both MIP-2 and KC activity indicating that chemokine levels were regulated by IL-1beta. These studies demonstrate that the regulation of MIP-2 activity may be beneficial in reducing corneal damage during microbial keratitis in rodents and perhaps that regulation of the human homologue of MIP-2, IL-8, may be useful for controlling keratitis in humans.