Immunoregulatory effects of testosterone supplementation combined with exercise training in men with Inclusion Body Myositis: a double-blind, placebo-controlled, cross-over trial.

Autor: Coudert JD; Centre for Molecular Medicine and Innovative Therapeutics Murdoch University Murdoch WA Australia.; Perron Institute for Neurological and Translational Science Nedlands WA Australia.; School of Medicine University of Notre Dame Fremantle WA Australia., Slater N; Centre for Molecular Medicine and Innovative Therapeutics Murdoch University Murdoch WA Australia., Sooda A; Centre for Molecular Medicine and Innovative Therapeutics Murdoch University Murdoch WA Australia., Beer K; Centre for Molecular Medicine and Innovative Therapeutics Murdoch University Murdoch WA Australia.; Perron Institute for Neurological and Translational Science Nedlands WA Australia., Lim EM; Department of Clinical Biochemistry, Pharmacology and Toxicology, PathWest Laboratory Medicine QEII Medical Centre Nedlands WA Australia., Boyder C; Department of Clinical Biochemistry, Pharmacology and Toxicology, PathWest Laboratory Medicine QEII Medical Centre Nedlands WA Australia., Zhang R; Department of Clinical Biochemistry, Pharmacology and Toxicology, PathWest Laboratory Medicine QEII Medical Centre Nedlands WA Australia., Mastaglia FL; Perron Institute for Neurological and Translational Science Nedlands WA Australia., Learmonth YC; Centre for Molecular Medicine and Innovative Therapeutics Murdoch University Murdoch WA Australia.; Perron Institute for Neurological and Translational Science Nedlands WA Australia.; Discipline of Exercise Science Murdoch University Murdoch WA Australia., Fairchild TJ; Centre for Molecular Medicine and Innovative Therapeutics Murdoch University Murdoch WA Australia.; Discipline of Exercise Science Murdoch University Murdoch WA Australia., Yeap BB; Medical School University of Western Australia Perth WA Australia.; Department of Endocrinology and Diabetes Fiona Stanley Hospital Perth WA Australia., Needham M; Centre for Molecular Medicine and Innovative Therapeutics Murdoch University Murdoch WA Australia.; Perron Institute for Neurological and Translational Science Nedlands WA Australia.; School of Medicine University of Notre Dame Fremantle WA Australia.; Department of Neurology Fiona Stanley Hospital Perth WA Australia.
Jazyk: angličtina
Zdroj: Clinical & translational immunology [Clin Transl Immunology] 2022 Sep 22; Vol. 11 (9), pp. e1416. Date of Electronic Publication: 2022 Sep 22 (Print Publication: 2022).
DOI: 10.1002/cti2.1416
Abstrakt: Objectives: Sporadic Inclusion Body Myositis (IBM) is an inflammatory muscle disease affecting individuals over the age of 45, leading to progressive muscle wasting, disability and loss of independence. Histologically, IBM is characterised by immune changes including myofibres expressing major histocompatibility complex molecules and invaded by CD8 + T cells and macrophages, and by degenerative changes including protein aggregates organised in inclusion bodies, rimmed vacuoles and mitochondrial abnormalities. There is currently no cure, and regular exercise is currently the only recognised treatment effective at limiting muscle weakening, atrophy and loss of function. Testosterone exerts anti-inflammatory effects, inhibiting effector T-cell differentiation and pro-inflammatory cytokine production.
Methods: We conducted a double-blind, placebo-controlled, cross-over trial in men with IBM, to assess whether a personalised progressive exercise training combined with application of testosterone, reduced the inflammatory immune response associated with this disease over and above exercise alone. To assess intervention efficacy, we immunophenotyped blood immune cells by flow cytometry, and measured serum cytokines and chemokines by Luminex immunoassay.
Results: Testosterone supplementation resulted in modest yet significant count reduction in the classical monocyte subset as well as eosinophils. Testosterone-independent immunoregulatory effects attributed to exercise included altered proportions of some monocyte, T- and B-cell subsets, and reduced IL-12, IL-17, TNF-α, MIP-1β and sICAM-1 in spite of interindividual variability.
Conclusion: Overall, our findings indicate anti-inflammatory effects of exercise training in IBM patients, whilst concomitant testosterone supplementation provides some additional changes. Further studies combining testosterone and exercise would be worthwhile in larger cohorts and longer testosterone administration periods.
Competing Interests: Active medication and placebo were provided without cost by Lawley Pharmaceuticals, Western Australia. BBY has received speaker honoraria and conference support from Bayer, Lilly and Besins, research support from Bayer, Lilly and Lawley Pharmaceuticals, and held advisory roles for Lilly, Besins, Ferring and Lawley Pharmaceuticals. The other authors have no competing interests to declare.
(© 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
Databáze: MEDLINE
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