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.
Berger
Ravi B
RB
Department of Ophthalmology, Case Western Reserve University and the Research Institute of University Hospitals of Cleveland, Cleveland, Ohio, USA.
Blackwell
Nathan M
NM
Lass
Jonathan H
JH
Diaconu
Eugenia
E
Pearlman
Eric
E
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