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D.J. Carr, J. Ash, J. Chodosh, T.E. Lane; Neutralizing Antibody to the Chemokine CXCL10 Reduces Ocular Inflammation and Delays Viral Spread Following Corneal HSV-1 Infection . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4183.
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Purpose:The inflammatory response to ocular herpes simplex virus type 1 (HSV-1) infection in mice is intense and is characterized by the production of soluble mediators. Production of pro-inflammatory cytokines and chemokines precedes and accompanies leukocyte infiltration into the eye. The present study was undertaken to determine the functional contributions of CXC chemokine ligand 10 (CXCL10) in initiating the inflammatory response to corneal infection with HSV-1. Methods:Female ICR mice (22-25 gms) were administered 100 µ g (intraperitoneally) of anti-CXCL10 neutralizing monoclonal antibody (IgG1) or control antibody (IgG) every other day for six days starting upon infection with HSV-1 (McKrae strain, 300 pfu/eye). The mice were assessed for cellular infiltration by slit lamp exam and immunohistochemical staining of tissue. In addition, viral titers were obtained from isolated corneal buttons, iris, retina, and trigeminal ganglia (TG) during the course of acute infection (days 1-7 post infection, p.i.). Finally, mice were monitored for cumulative survival. Results:Clinical scores of the mice day 5-6 p.i. by slit lamp exam revealed a significant reduction in pathology in the anti-CXCL10-treated mice having a mean score of 0.5-0.8 compared to 2.1-2.2 O.S. and O.D. respectively in the IgG control-treated mice. Such results coincided with a marked reduction in cellular infiltration in the stroma adjacent to the iris and ciliary body and reduced ICAM-1 transcript expression in the cornea of HSV-1-infected mice (3-6 days p.i.) treated with anti-CXCL10 antibody. Viral titers were elevated in the cornea of anti-CXCL10-treated mice early (day 3 p.i.) in infection. However, treatment of mice with anti-CXCL10 delayed the occurrence and yield of infectious virus in the retina and prolonged the cumulative survival of the infected mice. Conclusions: CXCL10 plays a pivotal role in orchestrating the inflammatory response to HSV-1 infection in the cornea. Moreover, these studies demonstrate a novel therapeutic method for treating ocular inflammatory disease by ablating chemokine function.
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