{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:55:59Z","timestamp":1774648559001,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Morphea\/localized scleroderma (LoS) represents an inflammatory-sclerotic skin disease, the pathogenesis of which is not fully understood. Given the important role of IL-1 family cytokines in the development and therapy of inflammatory diseases, including systemic sclerosis, we analyzed the clinical significance of serum levels of selected IL-1 family cytokines (IL-1\u03b1, IL-1\u03b2, IL-18, IL-33, IL-37 and IL-38) in LoS patients (n = 30) using the standardized disease assessment tools and comparison to healthy controls (n = 28). We also compared the pre- and post-treatment concentrations, i.e., before and after systemic (glucocorticosteroids and\/or methotrexate) and\/or topical (topical glucocorticosteroids and\/or calcineurin inhibitors). Our findings did not reveal significant differences in baseline IL-1\u03b1, IL-1\u03b2, IL-18, IL-33, IL-37 and IL-38 levels between LoS group and HCs; however, after treatment, there were marked changes in concentrations of IL-1\u03b1 and IL-33 within LoS group as well as in comparison to HCs. We also found significant negative correlations between PGA-A and IL-1\u03b1 concentration as well as between mLoSSI and IL-1\u03b1 after treatment. Furthermore, we showed an inverse correlation of baseline IL-1\u03b2 levels with mLoSSI scores of borderline significance. We believe that IL-1\u03b1 and IL-33, as well as Il-1\u03b2, may be potential mediators and targets of interest in LoS.<\/jats:p>","DOI":"10.3390\/jcm11216375","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T07:26:50Z","timestamp":1667114810000},"page":"6375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Serum Levels of Selected IL-1 Family Cytokines in Patients with Morphea"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-5407","authenticated-orcid":false,"given":"Paulina","family":"Szczepanik-Ku\u0142ak","sequence":"first","affiliation":[{"name":"Chair and Department of Dermatology, Venerology and Paediatric Dermatology, Medical University of Lublin, 20-081 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Michalska-Jakubus","sequence":"additional","affiliation":[{"name":"Chair and Department of Dermatology, Venerology and Paediatric Dermatology, Medical University of Lublin, 20-081 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Kowal","sequence":"additional","affiliation":[{"name":"Chair and Department of Dermatology, Venerology and Paediatric Dermatology, Medical University of Lublin, 20-081 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3176-9870","authenticated-orcid":false,"given":"Dorota","family":"Krasowska","sequence":"additional","affiliation":[{"name":"Chair and Department of Dermatology, Venerology and Paediatric Dermatology, Medical University of Lublin, 20-081 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Immunologic underpinnings and treatment of morphea","volume":"4","author":"LaChance","year":"2022","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/ddg.12724","article-title":"German guidelines for the diagnosis and therapy of localized scleroderma","volume":"14","author":"Kreuter","year":"2016","journal-title":"JDDG J. der Dtsch. Dermatol. Ges."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1093\/rheumatology\/27.4.286","article-title":"An epidemiological study of scleroderma in the West Midlands","volume":"27","author":"Silman","year":"1988","journal-title":"Rheumatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"333","DOI":"10.5114\/dr.2019.88252","article-title":"Localized scleroderma (morphea). Diagnostic and therapeutic recommendations of the Polish Dermatological Society","volume":"106","author":"Krasowska","year":"2019","journal-title":"Dermatol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/bjd.15001","article-title":"The molecular pathogenesis of morphoea: From genetics to future treatment targets","volume":"177","author":"Saracino","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00403-019-01991-0","article-title":"MicroRNA in localized scleroderma: A review of literature","volume":"312","author":"Krasowska","year":"2020","journal-title":"Arch. Dermatol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"437","DOI":"10.21037\/atm-20-6222","article-title":"Morphea: Progress to date and the road ahead","volume":"9","author":"Abbas","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1111\/jdv.14458","article-title":"European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes","volume":"31","author":"Knobler","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/rheumatology\/kep361","article-title":"Development and initial validation of the Localized Scleroderma Skin Damage Index and Physician Global Assessment of disease Damage: A proof-of-concept study","volume":"49","author":"Arkachaisri","year":"2010","journal-title":"Rheumatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12955-018-1010-z","article-title":"Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) adapted for use in adult patients: Report from an initial validation study","volume":"16","year":"2018","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nri2691","article-title":"The IL-1 family: Regulators of immunity","volume":"10","author":"Sims","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/ni1110-973","article-title":"IL-1 family nomenclature","volume":"11","author":"Dinarello","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-94-024-0921-5_2","article-title":"The Interleukin-1 Family","volume":"941","author":"Yazdi","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12621","article-title":"Overview of the IL-1 family in innate inflammation and acquired immunity","volume":"281","author":"Dinarello","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cyto.2011.04.001","article-title":"Cytokine profiles in localized scleroderma and relationship to clinical features","volume":"55","author":"Kurzinski","year":"2011","journal-title":"Cytokine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1159\/000071783","article-title":"Serum Levels of Tumor Necrosis Factor and Interleukin-13 are Elevated in Patients with Localized Scleroderma","volume":"207","author":"Hasegawa","year":"2003","journal-title":"Dermatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1001\/archderm.1994.01690100117021","article-title":"Demonstration of interleukin 8 in serum samples of patients with localized scleroderma","volume":"130","author":"Ihn","year":"1994","journal-title":"Arch. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/art.1780370618","article-title":"Serum levels of soluble interleukin-2 receptor","volume":"37","author":"Uziel","year":"1994","journal-title":"Arthritis Care Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S0190-9622(94)70221-7","article-title":"Increased levels of circulating intercellular adhesion molecule-1 in patients with localized scleroderma","volume":"31","author":"Ihn","year":"1994","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/BF01262331","article-title":"Demonstration of interleukin-2, interleukin-4 and interleukin-6 in sera from patients with localized scleroderma","volume":"287","author":"Ihn","year":"1995","journal-title":"Arch. Dermatol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/art.1780370218","article-title":"Immunocytochemical localization and serological detection of transforming growth factor \u03b21. Association with type I procollagen and inflammatory cell markers in diffuse and limited systemic sclerosis, morphea, and Raynaud\u2019s phenomenon","volume":"37","author":"Higley","year":"1994","journal-title":"Arthritis Care Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/j.1365-2133.1996.tb06313.x","article-title":"Clinical significance of serum levels of soluble interleukin-2 receptor in patients with localized scleroderma","volume":"134","author":"Ihn","year":"1996","journal-title":"Br. J. Dermatol."},{"key":"ref_23","first-page":"1917","article-title":"Serum levels of soluble interleukin 6 receptor and soluble gp130 are elevated in patients with localized scleroderma","volume":"27","author":"Nagaoka","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_24","first-page":"47","article-title":"Evaluation of serum concentrations of the selected cytokines in patients with localized scleroderma","volume":"33","author":"Kowal","year":"2016","journal-title":"Adv. Dermatol. Allergol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R188","DOI":"10.1186\/ar4378","article-title":"Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma","volume":"15","author":"Magee","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.semarthrit.2015.06.006","article-title":"Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma: T-helper cell-associated cytokine profiles","volume":"45","author":"Torok","year":"2015","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"247","DOI":"10.5114\/ceji.2012.30800","article-title":"Clinical immunology Interleukin 1\u03b2 in morphea","volume":"3","author":"Kowalczyk","year":"2012","journal-title":"Central Eur. J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.3389\/fimmu.2019.02025","article-title":"The Roles of IL-1 Family Cytokines in the Pathogenesis of Systemic Sclerosis","volume":"10","author":"Xu","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1007\/s10753-014-9848-7","article-title":"Association of Interleukin 1 Family with Systemic Sclerosis","volume":"37","author":"Zhang","year":"2014","journal-title":"Inflammation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"653950","DOI":"10.3389\/fimmu.2021.653950","article-title":"Interleukin-1 and Systemic Sclerosis: Getting to the Heart of Cardiac Involvement","volume":"12","author":"Cavalli","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jdermsci.2017.12.005","article-title":"Systemic sclerosis complicated with localized scleroderma-like lesions induced by K\u00f6bner phenomenon","volume":"89","author":"Saigusa","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"102763","DOI":"10.1016\/j.autrev.2021.102763","article-title":"Interleukin 1\u03b1: A comprehensive review on the role of IL-1\u03b1 in the pathogenesis and treatment of autoimmune and inflammatory diseases","volume":"20","author":"Cavalli","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3109\/s10165-011-0480-1","article-title":"Involvement of IL-33 in the pathogenesis of rheumatoid arthritis: The effect of etanercept on the serum levels of IL-33","volume":"22","author":"Kageyama","year":"2011","journal-title":"Mod. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/rheumatology\/kep402","article-title":"Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus","volume":"49","author":"Mok","year":"2009","journal-title":"Rheumatology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.3389\/fimmu.2018.02663","article-title":"Interleukin-33 in Systemic Sclerosis: Expression and Pathogenesis","volume":"9","author":"Li","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1172\/JCI4304","article-title":"Endogenous IL-1\u03b1 from systemic sclerosis fibroblasts induces IL-6 and PDGF-A","volume":"103","author":"Kawaguchi","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nm.2807","article-title":"Mechanisms of fibrosis: Therapeutic translation for fibrotic disease","volume":"18","author":"Wynn","year":"2012","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1006\/bbrc.1999.0155","article-title":"IL-1 Rescues Scleroderma Myofibroblasts from Serum-Starvation-Induced Cell Death","volume":"255","author":"Kirk","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","first-page":"182","article-title":"IL-1 and T Helper Immune Responses","volume":"15","author":"Santarlasci","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_40","first-page":"355","article-title":"Interleukin-1\u03b2 inhibits collagen synthesis and promotes its decomposition in cultured cardiac fibroblasts","volume":"60","author":"Xiao","year":"2008","journal-title":"Sheng Li Xue Bao"},{"key":"ref_41","first-page":"709","article-title":"Interleukin-1 inhibits the synthesis of collagen by fibroblasts","volume":"13","author":"Bhatnagar","year":"1986","journal-title":"Biochem. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.joen.2005.10.055","article-title":"Interleukin-1 \u03b1 Alters the Expression of Matrix Metalloproteinases and Collagen Degradation by Pulp Fibroblasts","volume":"32","author":"Wisithphrom","year":"2006","journal-title":"J. Endod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/S0140-6736(05)62472-5","article-title":"Induction of interstitial collagenase (MMP-1) by UVA-1 phototherapy in morphea fibroblasts","volume":"350","author":"Gruss","year":"1997","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Malewska-Wo\u017aniak, A., Lodyga, M., and Adamski, Z. (2022). Concentrations of metalloproteinase-1 in patients with morphea treated with phototherapy: A preliminary study. Adv. Dermatol. Allergol., 38.","DOI":"10.5114\/ada.2021.113127"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R17","DOI":"10.1186\/ar4444","article-title":"Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937","volume":"16","author":"Olsen","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_46","first-page":"176","article-title":"Inhibition by glucocorticoids of the formation of interleukin-1 alpha, interleukin-1 beta, and interleukin-6: Mediation by decreased mRNA stability","volume":"43","author":"Amano","year":"1993","journal-title":"Mol. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.1128\/IAI.73.6.3725-3733.2005","article-title":"Effects of Prednisolone Treatment on Cytokine Expression in Patients with Leprosy Type 1 Reactions","volume":"73","author":"Andersson","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2012.11.006","article-title":"IL-1 receptor 2 (IL-1R2) and its role in immune regulation","volume":"32","author":"Peters","year":"2013","journal-title":"Brain, Behav. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"364","DOI":"10.3389\/fimmu.2019.00364","article-title":"IL33: Roles in Allergic Inflammation and Therapeutic Perspectives","volume":"10","author":"Chan","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.jaad.2014.04.009","article-title":"The role of skin trauma in the distribution of morphea lesions: A cross-sectional survey of the Morphea in Adults and Children cohort IV","volume":"71","author":"Grabell","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_51","first-page":"467808","article-title":"Updates on Morphea: Role of Vascular Injury and Advances in Treatment","volume":"2013","author":"Tollefson","year":"2013","journal-title":"Autoimmune Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/1346-8138.14009","article-title":"Methotrexate, but not narrowband ultraviolet B radiation, suppresses interleukin-33 mRNA levels in psoriatic plaques and protein levels in serum of patients with psoriasis","volume":"45","author":"Meephansan","year":"2017","journal-title":"J. Dermatol."},{"key":"ref_53","first-page":"5","article-title":"Expression of NLRP3 inflammasome, cytokines and vascular mediators in the skin of systemic sclerosis patients","volume":"17","author":"Jara","year":"2015","journal-title":"Isr. Med. Assoc. J. IMAJ"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e1045","DOI":"10.1002\/cti2.1045","article-title":"Analysis of serum interleukin(IL)-1\u03b1, IL -1\u03b2 and IL -18 in patients with systemic sclerosis","volume":"8","author":"Lin","year":"2019","journal-title":"Clin. Transl. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1002\/art.23451","article-title":"Combined analysis of monocyte and lymphocyte messenger RNA expression with serum protein profiles in patients with scleroderma","volume":"58","author":"Duan","year":"2008","journal-title":"Arthritis Care Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/1346-8138.12011","article-title":"Serum levels of interleukin-1\u03b1 in patients with systemic sclerosis","volume":"40","author":"Maekawa","year":"2013","journal-title":"J. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/art.1780350111","article-title":"Interleukin-1, Interleukin-2, Interleukin-4, Interleukin-6, Tumor Necrosis Factor \u03b1, and Interferon-\u03b3 Levels in Sera from Patients with Scleroderma","volume":"35","author":"Needleman","year":"1992","journal-title":"Arthritis Care Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1136\/jcp.2004.019224","article-title":"Alterations of mononuclear inflammatory cells, CD4\/CD8+ T cells, interleukin 1, and tumour necrosis factor in the bronchoalveolar lavage fluid, peripheral blood, and skin of patients with systemic sclerosis","volume":"58","author":"Hussein","year":"2005","journal-title":"J. Clin. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00393-016-0202-3","article-title":"Elevated serum levels of interleukin-1\u03b2 and interleukin-33 in patients with systemic sclerosis in Chinese population","volume":"77","author":"Zhang","year":"2018","journal-title":"Z Rheumatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s10067-011-1686-5","article-title":"Serum IL-33 levels are raised in patients with systemic sclerosis: Association with extent of skin sclerosis and severity of pulmonary fibrosis","volume":"30","author":"Yanaba","year":"2011","journal-title":"Clin. Rheumatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/21\/6375\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:04:56Z","timestamp":1760144696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/21\/6375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,28]]},"references-count":60,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["jcm11216375"],"URL":"https:\/\/doi.org\/10.3390\/jcm11216375","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,28]]}}}