Interleukin-4-mediated infiltration of eosinophils into the conjunctiva and its suppression by interferon-gamma.
OBJECTIVE
Interleukin (IL)-4 is a T helper (Th)2 cytokine that plays an important role in the development of allergic reactions. It has been suggested that IL-4 is responsible for the infiltration of eosinophils into the conjunctiva during the development of allergic conjunctivitis. However, it is still unclear whether IL-4 is able to induce this eosinophilic infiltration on its own. We investigated whether subconjunctival injection of IL-4 can induce eosinophils to infiltrate into the conjunctiva.


METHODS
Brown Norway rats were subconjunctivally injected with IL-4, eotaxin, or phosphate buffered saline (PBS), and the conjunctivas were harvested for histologic analysis (including immunohistochemistry) 6, 12, 18, and 24 hr later. The harvested conjunctivas were also subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to examine chemokine expression. In a separate experiment, the effect of coadministering interferon-gamma (IFN-gamma) along with IL-4 was examined.


RESULTS
The subconjunctival injection of IL-4 induced eosinophil infiltration into the conjunctiva in a dose-dependent manner. IL-4 was as potent as eotaxin. The eosinophilic infiltration started 6 hr after the injection and persisted for up to 24 hr after the injection. Other infiltrating cell phenotypes were noted but were also observed in conjunctivas injected with PBS alone. RT-PCR analysis demonstrated that IL-4 injection did not upregulate chemokine RNA expression in the conjunctiva. Coinjection of IFN-gamma suppressed the infiltration of eosinophils into the conjunctiva induced by IL-4 injection.


CONCLUSIONS
The subconjunctival injection of IL-4 specifically induces eosinophils to infiltrate into the conjunctiva. In addition, IFN-gamma in the conjunctiva can counteract this effect of IL-4.
Fukushima
Atsuki
A
Department of Ophthalmology, Kochi Medical School, Kohasu, Nankoku-city, Japan. fukusima@med.kochi-u.ac.jp
Jian
Zhang
Z
Ishida
Waka
W
Fukata
Kazuyo
K
Ozaki
Akemi
A
Ueno
Hisayuki
H
D000818:Animals; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects*; D054413:Chemokine CCL11; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000494:pharmacology; D003228:Conjunctiva / Q000166:cytology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004804:Eosinophils / Q000502:physiology*; D007267:Injections; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C515458:Ccl11 protein, rat; D054413:Chemokine CCL11; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D004338:Drug Combinations; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma