Exacerbation of Acanthamoeba keratitis in animals treated with anti-macrophage inflammatory protein 2 or antineutrophil antibodies

Neutrophils are thought to be involved in many infectious diseases and have been found in high numbers in the corneas of patients with Acanthamoeba ke ratitis, Using a Chinese hamster model of keratitis, conjunctival neutrophi l migration was manipulated to determine the importance of neutrophils in t his disease. Inhibition of neutrophil recruitment was achieved by subconjun ctival injection with an antibody against macrophage inflammatory protein 2 (MIP-2), a powerful chemotactic factor for neutrophils which is secreted b y the cornea. In other experiments, neutrophils were depleted by intraperit oneal injection of anti-Chinese hamster neutrophil antibody. The inhibition of neutrophils to the cornea resulted in an earlier onset and more severe infection compared to controls. Anti MIP-2 antibody treatment produced an a lmost 35% reduction of myeloperoxidase activity in the cornea 6 days postin fection, while levels of endogenous MIP-2 secretion increased significantly . Recruitment of neutrophils into the cornea cia intrastromal injections of recombinant MIP-2 generated an initially intense inflammation that resulte d in the rapid resolution of the corneal infection. The profound exacerbati on of Acanthamoeba keratitis seen when neutrophil migration was inhibited? combined with the rapid clearing of the disease in the presence of increase d neutrophils, strongly suggests that neutrophils play an important role in combating Acanthamoeba infections in the cornea.