Intravenous glucocorticosteroid treatment augments apoptosis of inflammatory T cells in experimental autoimmune neuritis (EAN) of the Lewis rat.
Apoptosis plays a critical role in natural recovery from experimental autoimmune disorders of the nervous system. Here we investigated in experimental autoimmune neuritis (EAN) whether apoptosis is augmented by high-dose corticosteroids, the mainstay of therapeutically active compounds in this group of disorders. Adoptive transfer EAN was induced by intravenous injection of P2-specific T cell blasts. At disease onset or at the maximum of disease two pulses of steroids were given within 12 hours, and animals were sacrificed 6 hours later. Steroid therapy significantly reduced T cell infiltration in sciatic nerve. Treatment on both day 4 and day 7 caused a significant increase of T cell apoptosis (42% vs 8.4% in placebo-treated animals on day 4, p < 0.05; 22.5% vs 7.0% on day 7, p < 0.05) in sciatic nerve as assessed by molecular labeling techniques. In addition, reduction of body weight and thymus weight and augmentation of thymocyte apoptosis were observed in steroid recipients. Steroid treatment markedly reduced cellular proliferation in lymphoid organs as measured by bromodeoxyuridine incorporation. Glucocorticosteroid treatment augments T cell apoptosis in inflammatory lesions of the peripheral nervous system, and this may add to their anti-inflammatory properties mediated by downregulation of cytokine expression.
Zettl
U K
UK
Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
Gold
R
R
Toyka
K V
KV
Hartung
H P
HP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D005260:Female; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D007275:Injections, Intravenous; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000473:pathology; D013154:Spleen / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
D011239:Prednisolone; C021322:prednisolone hemisuccinate