Expression of interleukin-18 in muscle tissue of patients with polymyositis or dermatomyositis and effects of conventional immunosuppressive treatment

Helmers, S. B., Bruton, M., Loell, I., Ulfgren, A.-K., Gracie, A. J., McInnes, I. B. and Lundberg, I. E. (2018) Expression of interleukin-18 in muscle tissue of patients with polymyositis or dermatomyositis and effects of conventional immunosuppressive treatment. Rheumatology, 57(12), pp. 2149-2157. (doi: 10.1093/rheumatology/key222) (PMID:30102381)

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Abstract

Objectives: To investigate the expression of IL-18 in symptomatic and asymptomatic muscle tissues of patients with PM and DM and the effects of conventional immunosuppressive treatment on such expression. Methods: Two cohorts of patients were included in this study. The first cohort consisted of 10 new-onset myositis patients. IL-18 expression was compared between symptomatic and asymptomatic muscle biopsies that were taken prior to treatment. The second cohort consisted of another 10 patients with repeated muscle biopsies before and after 8 months with conventional immunosuppressive treatment. Using immunohistochemistry, IL-18 expression in muscle tissues was compared before and after treatment. Biopsies from seven healthy individuals were included as controls. Results: IL-18 expression was predominantly localized to inflammatory cells and capillaries in patients and mostly to capillaries in healthy controls. Total IL-18 expression in muscle tissues from the new-onset patients, at both symptomatic and asymptomatic sites, was significantly higher compared with healthy controls (P = 0.007 and P = 0.002) with no statistical difference in appearances between symptomatic and asymptomatic sites. The number of IL-18 positive capillaries was not different among symptomatic, asymptomatic and healthy muscles. Total IL-18 expression appeared lower in biopsies from patients receiving and improving with immunosuppressive treatment, particularly the number of IL-18 positive inflammatory cells but not the number of IL-18 positive capillaries, which was consistent with significantly decreased expression of CD68+ macrophages (P = 0.04). Conclusion: IL-18 is highly expressed in muscle tissue in the context of inflammatory myopathies and based on its plausible effector functions could provide a novel therapeutic target in future.

Item Type:Articles
Additional Information:This work was supported by grants from the Swedish Rheumatism Association, King Gustaf Vth 80-year Foundation and the Swedish Research Council K2014-52X-14045-14, Inger Bedix Association for medical research and through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain
Authors: Helmers, S. B., Bruton, M., Loell, I., Ulfgren, A.-K., Gracie, A. J., McInnes, I. B., and Lundberg, I. E.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Rheumatology
Publisher:Oxford University Press (OUP)
ISSN:1462-0324
ISSN (Online):1462-0332

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