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2001 Ocular Microbiology and Immunology Group, Abstract 6

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IL-4 and IL-13 Mediated Recruitment of Eosinophils into the Cornea in a Mouse Model of Onchocerca volvulus keratitis (River Blindness)
R.B. Berger1, E. Diaconu1,2, N.M. Blackwell2, E. Pearlman1,2 and J.H. Lass1
Departments of Ophthalmology1 and Medicine2, Case Western University and University Hospitals of Cleveland, Cleveland OH

Purpose: To examine the role of IL-4 and IL-13 as local effectors of Th2-mediated inflammation in a mouse model of 0.Volvulus-mediated keratitis.

Methods: Immunized mice were challenged by intrastromal injection of 10µg of soluble 0.volvulus antigen. In addition they received injections of a soluble form of the IL-13 receptor (sIL-13a2.Fc), anti-IL-4 mAb (11B11), or both in the right subconjunctival space. Left eyes served as internal control, receiving an inactive human and/or rat IgG in the left subconjunctival space. Eosinophil infiltration into the cornea, and the relative expression of the adhesion molecules ICAM-1 and VCAM-1 in the limbal vessels were determined by immunohistochemistry.

Results: Following intrastromal injection of C.volvulus antigen into the cornea, eosinophil infiltration was reduced by almost half at both 24h and 72h post challenge in eyes treated with anti-IL-4 mAb. Eyes treated with anti-IL-13 demonstrated a similar reduction in eosinophil recruitment at 24 hours compared to controls, but not at 72h post challenge. When both cytokines were neutralized simultaneously, we observed a synergistic reduction in eosiniphil infiltration at all time points following intrastromal challenge. The site of activity appeared to be from limbal vessels to central cornea. In addition, local neutralization of IL-4 and IL-13 differentially reduced limbal expression of ICAM-1 and VCAM-1, which are important in the tethering of eosinophils to the vascular endothelium of the limbal vessels for subsequent transmigration into the cornea.

Conclusions: Results of the current study demonstrate a synergistic role for IL-4 and IL-13 in effecting eosinophil recruitment into the cornea in 0.volvulus-mediated keratitis, and may be a target for immune intervention for eosinophil related ocular inflammation.

Financial Support: Research to Prevent Blindness (RB and JHL) and the National Eye Institute EY10320 (EP) and EY1173-01 (JHL).

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