Department of Dermatology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan.
Exp Dermatol. 2024 Jun;33(6):e15115. doi: 10.1111/exd.15115.
Itchy skin or pruritus is a common cutaneous symptom that causes an urge to scratch, and the role of interleukins (IL) in itchy skin has been widely studied. IL-4 and IL-13 are known to induce chronic itch. Similarly, the direct role of IL-31 in inducing itch has been demonstrated in clinical situations such as atopic dermatitis and prurigo nodularis. Moreover, IL-4 receptor α antibodies (dupilumab) and IL-31 receptor A antibodies (nemolizumab) inhibit pruritus. However, the interplay between these ILs in pruritus remains unclear. Therefore, we investigated the reciprocal effects of these cytokines on pruritus in mice. The intradermal administration of IL-31 induced itch-associated scratching behaviour in a dose-dependent manner. Interestingly, the amount of IL-31 and IL-4/IL-13, co-administration or 30 min pre-administration of IL-4/IL-13 and intradermal or intravenous pre-administration of IL-4 did not affect IL-31-induced itch-associated scratching behaviour when it was observed for 30 min, 2 h, 24 h or 48 h. Pre-administration of neutralising antibodies against IL-4 and IL-13 also did not affect IL-31-induced itch-associated scratching behaviour. These results suggest that IL-31 can induce itching independently of IL-4 and IL-13 in vivo.
皮肤瘙痒或瘙痒是一种常见的皮肤症状，会引起搔抓的冲动，白细胞介素（IL）在皮肤瘙痒中的作用已得到广泛研究。已知白细胞介素 4（IL-4）和白细胞介素 13（IL-13）可诱导慢性瘙痒。同样，白细胞介素 31（IL-31）在特应性皮炎和结节性痒疹等临床情况下诱导瘙痒的直接作用也已得到证实。此外，白细胞介素 4 受体α抗体（度普利尤单抗）和白细胞介素 31 受体 A 抗体（奈莫利尤单抗）可抑制瘙痒。然而，这些白细胞介素在瘙痒中的相互作用尚不清楚。因此，我们研究了这些细胞因子在小鼠瘙痒中的相互作用。白细胞介素 31 的皮内给药以剂量依赖性方式诱导瘙痒相关的搔抓行为。有趣的是，当观察 30 分钟、2 小时、24 小时或 48 小时时，IL-31 和 IL-4/IL-13 的共同给药或 IL-4/IL-13 的 30 分钟预给药以及 IL-4 的皮内或静脉内预给药均不会影响 IL-31 诱导的瘙痒相关搔抓行为。针对 IL-4 和 IL-13 的中和抗体的预给药也不会影响 IL-31 诱导的瘙痒相关搔抓行为。这些结果表明，白细胞介素 31 可在体内独立于白细胞介素 4 和白细胞介素 13 诱导瘙痒。
