Mononuclear cell analysis of muscle biopsies in prednisone- and azathioprine-treated Duchenne muscular dystrophy.
Prednisone improves strength and function in patients with Duchenne dystrophy. Although the mechanism of this effect is uncertain, prior studies suggested that the benefit might result from immunosuppressive effects on T lymphocytes invading muscle. A recent randomized, double-blind, controlled trial of prednisone and azathioprine demonstrated that azathioprine had no effect in Duchenne dystrophy, raising questions about the role of immunosuppression in mediating clinical improvement. The goal of this current study was to compare the effects of prednisone and azathioprine on mononuclear infiltrates from biopsies performed at the end of the controlled clinical trial (reported separately in the article by Griggs et al on page 520). We studied 14 patients from the prednisone group (0.75 mg/kg/d), 10 from the combination therapy group (prednisone 0.3 mg/kg/d and azathioprine 2.5 mg/kg/d), and 13 from the azathioprine group (2.5 mg/kg/d), and used monoclonal antibodies for cell typing. There were no significant differences between the groups for total T cells, T-cell subsets, B cells, natural killer cells, total mononuclear cells, necrotic muscle fibers, or fibers focally invaded by mononuclear cells. These data indicate that azathioprine decreases mononuclear subsets infiltrating muscle to a similar degree as does prednisone, although azathioprine-treated patients do not show a clinical improvement. This implies that immunosuppressive actions on cellular infiltrates in muscle are probably not the primary mechanism of prednisone-induced clinical improvement.
Kissel
J T
JT
Department of Neurology, Ohio State University, Columbus.
Lynn
D J
DJ
Rammohan
K W
KW
Klein
J P
JP
Griggs
R C
RC
Moxley
R T
RT
Cwik
V A
VA
Brooke
M H
MH
Mendell
J R
JR
D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis; D001379:Azathioprine / Q000008:administration & dosage* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects*; D009136:Muscular Dystrophies / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010919:Placebos; D011241:Prednisone / Q000008:administration & dosage* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects*
D015703:Antigens, CD; D010919:Placebos; D001379:Azathioprine; D011241:Prednisone