Enigmatic Role of IL-31 in the Itch and Inflammation of Vernal Keratoconjunctivitis.

Vernal keratoconjunctivitis (VKC) is a recurrent allergic inflammation of the conjunctiva characterized by itchiness. The cytokine IL-31 is involved in itch and inflammation in other conditions, so we investigated whether it plays similar role in VKC. We estimated messenger RNA (mRNA) IL-31 expression in giant papillae (GP) with real-time polymerase chain reaction (RT-PCR). We used immunohistochemistry to examine IL-31 receptor (IL-31R) expression in neurons and epithelial cells in GP. We then performed fluorescence-activated cell sorting and immunofluorescence to examine IL-31R expression in cultured human conjunctival epithelial cells (HConEpiCs) either treated or not treated with various cytokines. Next, we examined the expression of phosphorylated signal transducer and activator of transcription 3 (P-STAT3) and suppressor of cytokine signaling 3 (SOCS3) in the epithelium of GP and control specimens using immunohistochemistry. Last, we used DNA microarray analysis and RT-PCR to investigate whether recombinant IL-31 induced expression of various genes in HConEpiCs. IL-31 expression was elevated in GP compared with control specimens. Although many neuron fibers innervated GP, none was found to express IL-31R. IL-31R was expressed in the epithelium of GP and in HConEpiCs, and its expression in HConEpiCs was not altered by any of the investigated cytokines. Recombinant IL-31 increased SOCS3 mRNA expression. Strong P-STAT3 expression was observed in the epithelium of GP, but SOCS3 expression was not observed. Increased IL-31 in GP of VKC patients may not directly influence itch sensation via neuron fibers and inflammation via the expression of P-STAT3 and SOCS3.