IL-4 and IL-13 regulation of ICAM-1 expression and eosinophil recruitment in Onchocerca volvulus keratitis.
OBJECTIVE
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.
Department of Ophthalmology, Case Western Reserve University and the Research Institute of University Hospitals of Cleveland, Cleveland, Ohio, USA.
Ravi B
RB
Berger
Nathan M
NM
Blackwell
Jonathan H
JH
Lass
Eugenia
E
Diaconu
Eric
E
Pearlman
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D003319:Corneal Stroma / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D018793:Interleukin-13 / Q000008:administration & dosage / Q000502:physiology*; D015847:Interleukin-4 / Q000008:administration & dosage / Q000502:physiology*; D007634:Keratitis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D017181:Onchocerca volvulus / Q000502:physiology; D015827:Onchocerciasis, Ocular / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D011994:Recombinant Proteins
D018793:Interleukin-13; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4