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Hussein, M.R. et al.

The effects of glucocorticoid therapy on the inflammatory and dendritic cells in muscular dystrophies.

Various clinical trials have documented the therapeutic benefit of glucocorticoids (GCs) in enhancing muscle strength and slowing disease progression of Duchenne and Becker muscular dystrophies ( DMD/ BMD). We hypothesized that GCs may have relevance to the differential anti-inflammatory effect on mononuclear inflammatory cells (MICs) and Dendritic cells (DCs) infiltrating the dystrophic muscles. In this prospective study, two muscle biopsies were obtained (before and after 6-month prednisone therapy) from 30 patients with dystrophies ( DMD = 18; BMD = 6; and limb girdle muscular dystrophies (LGMD) = 6). MICs and DCs infiltrating the muscles were examined using mouse monoclonal antibodies and immunoperoxidase staining methods. Muscle strength was evaluated monthly by manual testing, motor ability and timed tests. Prednisone therapy was associated with: (i) functional improvement of overall motor disability, in upper limbs of DMD (P < 0.001) and BMD (P < 0.01) and lower limbs of DMD (P < 0.001) and BMD (P < 0.05); (ii) histological improvement such as fibre size variation ( DMD, P < 0.01; BMD, P < 0.05), internalization of nuclei ( DMD, P < 0.05), degeneration and necrosis ( DMD and BMD, P < 0.01), regeneration ( DMD, P < 0.001; BMD, P < 0.01) and endomysial connective tissue proliferation ( DMD, P < 0.01; BMD, P < 0.05) and (iii) reduction of total MICs (P < 0.01) and DCs (P < 0.01). There was a positive correlation between the degree of improvement in overall motor disability and reduction of DCs numbers (In upper limbs; r = 0.638, P < 0.01 for DMD and r = 0.725, P < 0.01 for BMD, in Lower limbs; r = 0.547, P < 0.05 for DMD and r = 0.576, P < 0.05 for BMD). Such improvements and changes of MICs/DCs were absent in LGMD. In DMD/ BMD, prednisone therapeutic effect was associated with reduced MICs and DCs numbers. Whether this therapeutic effect reflects targeting of the deleterious immune response produced by these cells mandates further investigations.[1]

References

The effects of glucocorticoid therapy on the inflammatory and dendritic cells in muscular dystrophies. Hussein, M.R., Hamed, S.A., Mostafa, M.G., Abu-Dief, E.E., Kamel, N.F., Kandil, M.R. International journal of experimental pathology (2006) [Pubmed]

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