Musolino Caterina, Allegra Alessandro, Mannucci Carmen, Russo Sabina, Alonci Andrea, Maisano Valerio, Calapai Gioacchino, Gangemi Sebastiano
University of Messina Faculty of Medicine, Department of General Surgery and Oncology, Division of Hematology, Messina, Italy Phone: 0039 090 221 23 64 E-mail:
Turk J Haematol. 2015 Jun;32(2):168-71. doi: 10.4274/tjh.2014.0021.
Imatinib mesylate is a small-molecule tyrosine kinase inhibitor (TKi) designed to target c-ABL and BCR-ABL, approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Adverse cutaneous reactions induced by imatinib are frequent, generally moderate, and dose-dependent. The aim of this work was to investigate the possible contribution of interleukin (IL)-33 and IL-31, cytokines involved in disorders associated with itching, in the pathogenesis of pruritus in a patient undergoing imatinib mesylate treatment. His IL-31 and IL-33 serum levels were significantly higher than in the control group (respectively 96.6 pg/mL vs. 7.623±7.681 pg/mL and 27.566 pg/mL vs. 6.170±7.060 pg/mL). In light of these findings, imatinib mesylate-related symptoms of dermatologic toxicities might be related to the release of IL-31 and IL-33. In particular, it is supposable that TKi usage could cause keratinocyte injury, the release of IL-33, and the consequent interaction with its receptor on mast cells that induces the secretion of several factors capable of causing skin manifestations, including IL-31, a known pruritus-inducing cytokine. This report, to the best of our knowledge, is the first work describing the possible involvement of the IL-31/IL-33 axis in the pathogenesis of skin side effects related to imatinib mesylate treatment.
甲磺酸伊马替尼是一种旨在靶向c-ABL和BCR-ABL的小分子酪氨酸激酶抑制剂（TKi），被批准用于治疗慢性粒细胞白血病和胃肠道间质瘤。甲磺酸伊马替尼引起的皮肤不良反应很常见，一般为中度，且与剂量相关。这项研究的目的是调查白细胞介素（IL）-33和IL-31这两种与瘙痒相关疾病有关的细胞因子在接受甲磺酸伊马替尼治疗的患者瘙痒发病机制中可能发挥的作用。该患者的IL-31和IL-33血清水平显著高于对照组（分别为96.6 pg/mL对比7.623±7.681 pg/mL以及27.566 pg/mL对比6.170±7.060 pg/mL）。鉴于这些发现，甲磺酸伊马替尼相关的皮肤毒性症状可能与IL-31和IL-33的释放有关。特别是，可以推测TKi的使用可能导致角质形成细胞损伤、IL-33的释放，以及随后与肥大细胞上其受体的相互作用，从而诱导多种能够引起皮肤表现的因子的分泌，包括已知的诱导瘙痒的细胞因子IL-31。据我们所知，本报告是首篇描述IL-31/IL-33轴可能参与甲磺酸伊马替尼治疗相关皮肤副作用发病机制的研究。
