title: Possible Role of Interleukin-31/33 Axis in Imatinib Mesylate-Associated Skin Toxicity.
abstract: 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.
authors: Caterina
authors: C
authors: Musolino
authors: 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: aallegra@unime.it.
authors: Alessandro
authors: A
authors: Allegra
authors: Carmen
authors: C
authors: Mannucci
authors: Sabina
authors: S
authors: Russo
authors: Andrea
authors: A
authors: Alonci
authors: Valerio
authors: V
authors: Maisano
authors: Gioacchino
authors: G
authors: Calapai
authors: Sebastiano
authors: S
authors: Gangemi
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003875:Drug Eruptions / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000009:adverse effects* / Q000627:therapeutic use; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000502:physiology; D000067596:Interleukin-33 / Q000097:blood / Q000502:physiology*; D007378:Interleukins / Q000097:blood / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011537:Pruritus / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents; C079241:IL1RL1 protein, human; C502187:IL31 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate