ISSN: 1300-7777 E-ISSN: 1308-5263
Possible Role of Interleukin-31/33 Axis in Imatinib Mesylate-Associated Skin Toxicity [Turk J Hematol]
Turk J Hematol. 2015; 32(2): 168-171 | DOI: 10.4274/Tjh.2014.0021  

Possible Role of Interleukin-31/33 Axis in Imatinib Mesylate-Associated Skin Toxicity

Caterina Musolino1, Alessandro Allegra1, Carmen Mannucci2, Sabina Russo1, Andrea Alonci1, Valerio Maisano1, Gioacchino Calapai2, Sebastiano Gangemi3
1University of Messina Faculty of Medicine, Department of General Surgery and Oncology, Division of Hematology, Messina, Italy
2Azienda Ospedaliera Universitaria Policlinico “G. Martino”, Department of Clinical and Experimental Medicine, Operative Unit of Clinical Pharmacology, Messina, Italy
3University Of Messina Faculty Of Medicine, Policlinic “g. Martino”, Department Of Clinical And Experimental Medicine, Division Of Allergy And Clinical Immunology, Messina, Italy; Ifc Cnr, Messina Unit, Institute Of Clinical Physiology, Messina, Italy

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.

Keywords: Interleukin-31 (IL-31), Interleukin-33 (IL-33), Tyrosine kinase inhibitors, Imatinib mesylate, Chronic myeloid leukemia, Pruritus


İmatinib Mesilat ile İlişkili Deri Toksisitesinde İnterlökin-31/33 Aksının Olası Rolü

Caterina Musolino1, Alessandro Allegra1, Carmen Mannucci2, Sabina Russo1, Andrea Alonci1, Valerio Maisano1, Gioacchino Calapai2, Sebastiano Gangemi3
1University of Messina Faculty of Medicine, Department of General Surgery and Oncology, Division of Hematology, Messina, Italy
2Azienda Ospedaliera Universitaria Policlinico “G. Martino”, Department of Clinical and Experimental Medicine, Operative Unit of Clinical Pharmacology, Messina, Italy
3University Of Messina Faculty Of Medicine, Policlinic “g. Martino”, Department Of Clinical And Experimental Medicine, Division Of Allergy And Clinical Immunology, Messina, Italy; Ifc Cnr, Messina Unit, Institute Of Clinical Physiology, Messina, Italy

İmatinib mesilat c-ABL ve BCR-ABL’yi hedeflemek için tasarlanan küçük- molekül tirozin kinaz inhibitörü (TKİ) olup kronik miyeloid lösemi ve gastrointestinal stromal tümör tedavisi için onaylanmıştır. İmatinib ile indüklenen advers kutanöz reaksiyonlar nadir, genellikle ılımlı ve doz bağımlıdır. Bu çalışmanın amacı, kaşıntı ile ilişkili bozukluklar ile ilgili sitokinler olan interlökin (IL)-33 ve IL-31’in imatinib mesilat tedavisi alan bir hastada kaşıntı patogenezine olası katkısını araştırmak idi. Hastanın serum IL-31 ve IL-33 düzeyleri kontrol grubundan anlamlı olarak yüksek idi (sırasıyla; 96,6 pg/mL vs. 7,623±7,681 pg/mL ve 27,566 pg/mL vs. 6,170±7,060 pg/mL). Bu bulgular ışığında, imatinib mesilatile ilişkili dermatolojik toksisiteler IL-31 ve IL-33 salınımı ile ilişkili olabilir. Özellikle, TKİ kullanımının keratinosit hasarı, IL-33 salınımı ve mast hücre yüzeyindeki reseptörü ile karşılıklı etkileşimi sonucu, deri bulgularına yol açma yeteneği olan, kaşıntıyı-indükleyen bir sitokin olarak bilinen IL-31’de içeren çeşitli faktörlerin sekresyonuna sebep olabileceği varsayılabilir. Bu rapor, bildiğimizce, imatinin mesilat tedavisi ile ilişkili deri yan etkilerinin patogenezinde interlökin-31/33 aksının olası rolünü tanımlayan ilk çalışmadır.

Anahtar Kelimeler: İnterlökin-31 (IL-31), İnterlökin-33 (IL-33), Tirozin kinaz inhibitörleri, İmatinib mesilat, Kronik miyeloid lösemi, Kaşıntı


Caterina Musolino, Alessandro Allegra, Carmen Mannucci, Sabina Russo, Andrea Alonci, Valerio Maisano, Gioacchino Calapai, Sebastiano Gangemi. Possible Role of Interleukin-31/33 Axis in Imatinib Mesylate-Associated Skin Toxicity. Turk J Hematol. 2015; 32(2): 168-171

Corresponding Author: Alessandro Allegra, Italy


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