Interleukin-4–Mediated Infiltration of Eosinophils into the Conjunctiva and Its Suppression by Interferon-γ

Abstract

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-γ (IFN-γ) 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-γ 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-γ in the conjunctiva can counteract this effect of IL-4.

Keywords:

• allergy;
• conjunctiva;
• interferon-gamma;
• interleukin-4