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

• Published in: Clinical & translational immunology Vol. 11; no. 9; pp. e1416 - n/a
• Main Authors: Coudert, Jerome D, Slater, Nataliya, Sooda, Anuradha, Beer, Kelly, Lim, Ee Mun, Boyder, Conchita, Zhang, Rui, Mastaglia, Frank L, Learmonth, Yvonne C, Fairchild, Timothy J, Yeap, Bu B, Needham, Merrilee
• Format: Journal Article
• Language: English
• Published: Milton, Queensland John Wiley & Sons, Inc 2022; Wiley
• Subjects: Adenosine; Atrophy; autoimmunity; CD8 antigen; Cell differentiation; Chemokines; clinical trial; Cytokines; Double-blind studies; exercise therapy; Fitness training programs; Flow cytometry; Immunoregulation; Inclusion bodies; Inclusion Body Myositis; Inflammatory diseases; Leukocytes (eosinophilic); Lymphocytes; Lymphocytes T; Macrophages; Major histocompatibility complex; Middle age; Mitochondria; Monocytes; Musculoskeletal diseases; Musculoskeletal system; Myositis; Older people; Patients; Physical training; Placebos; Supplements; Testosterone; Tumor necrosis factor; Tumor necrosis factor-TNF; Vacuoles
• ISSN: 2050-0068; 2050-0068
• DOI: 10.1002/cti2.1416

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. This is a double‐blind, placebo‐controlled, cross‐over trial in 14 men with IBM, to assess whether a personalised progressive exercise training combined with topical application of testosterone, reduced the inflammatory immune response associated with this disease over and above exercise alone. Testosterone supplementation resulted in significant reduction in the classical monocyte subset as well as eosinophils, and of MIP‐1β. Testosterone‐independent immunoregulatory effects attributed to exercise included altered proportions of monocyte, T and B cell subsets, and reduced concentrations of pro‐inflammatory IL‐12, IL‐17, TNF‐α and sICAM‐1.