Interleukin-4-mediated infiltration of eosinophils into the conjunctiva and its suppression by interferon-γ

Purpose: 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.