Transcription of interleukin 31 and its receptor by leukocytes after Culicoides sp stimulation is dose dependent but is not exaggerated in allergic horses or correlated with pruritus

Abstract

OBJECTIVE Preliminary evidence supports a role for IL-31 in equine insect bite hypersensitivity (IBH) and pruritus. Our studies investigated IL-31 and IL-31 receptor-α (IL-31RA) transcription in leukocytes from normal and IBH horses in response to Culicoides nubeculosus. ANIMALS 19 normal and 15 IBH horses were recruited in the summer of 2019 (low-dose study) and 8 normal and 10 IBH horses in the winter of 2022 to 2023 (high-dose study). Normal horses had no history or signs of allergic skin disease, while IBH horses had a history and clinical signs compatible with IBH. Pruritus was scored using a visual analog score or a 1 to 6 grading system. PROCEDURES Whole blood leukocytes were incubated with saline (0.9% NaCl) solution or C nubeculosus (0.26 µg/mL [low dose]; 5 μg/mL [high dose]). Transcription of IL-31 and IL-31RA was measured by quantitative RT-PCR. RESULTS Transcription of IL-31 and IL-31RA significantly increased in leukocytes from normal and IBH horses following high-dose C nubeculosus, and no differences were found between populations. Following low-dose C nubeculosus IL-31RA, transcription was increased in both normal and IBH horses, but IL-31 transcription was reduced in normal horses. No positive correlation was found between pruritus scores and IL-31 transcription after low- or high-dose C nubeculosus stimulation. CLINICAL RELEVANCE Exaggerated IL-31 transcription was not identified in IBH horses, suggesting that dysregulation in IL-31 signaling occurs downstream or in localized tissues or involves regulation by yet unidentified receptor splice variants or IL-31-induced increased sensitivity to other pruritogens. Further studies to understand IL-31 signaling in equine allergic skin disease are needed.