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(Investigative Ophthalmology and Visual Science. 2002;43:2992-2997.)
© 2002 by The Association for Research in Vision and Ophthalmology, Inc.

IL-4 and IL-13 Regulation of ICAM-1 Expression and Eosinophil Recruitment in Onchocerca volvulus Keratitis

Ravi B. Berger1, Nathan M. Blackwell2, Jonathan H. Lass1, Eugenia Diaconu1,2 and Eric Pearlman1,2

1 From the Departments of Ophthalmology and 2 Medicine, Case Western Reserve University and the Research Institute of University Hospitals of Cleveland, Cleveland, Ohio.

PURPOSE. The presence of eosinophilic granulocytes in ocular tissue is a hallmark of the host response to environmental and parasite allergens. Using a mouse model of Onchocerca volvulus–mediated keratitis (river blindness), the present study examined the role of the cytokines interleukin (IL)-4 and IL-13 in regulating recruitment of eosinophils to the cornea through expression of intercellular cell adhesion molecule (ICAM)-1.

METHODS. C57BL/6 mice received an intrastromal injection of recombinant IL-4 and IL-13 (rIL-4 and IL-13) or were immunized by subcutaneous injection prior to receiving an intrastromal injection of a soluble O. volvulus extract. Expression of ICAM-1 and recruitment of eosinophils to the cornea were monitored by immunohistochemistry.

RESULTS. Expression of ICAM-1 was elevated after injection of rIL-4 or IL-13 together with recombinant tumor necrosis factor (rTNF)-{alpha}. Conversely, expression of ICAM-1 in O. volvulus–mediated keratitis was significantly reduced after subconjunctival injection of a monoclonal antibody (mAb) to IL-4 or IL-13. In addition, combined in vivo neutralization of IL-4 and IL-13 inhibited recruitment of eosinophils, but not of neutrophils, to the corneal stroma.

CONCLUSIONS. These findings demonstrate that expression of ICAM-1 and recruitment of eosinophils to the cornea are tightly regulated by IL-4 and IL-13, and indicate that these cytokines are a potential target for immune intervention in ocular allergy and parasitic infections of the eye.




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