Effects of deflazacort and cortisone on cellular proliferation in the rat thymus.
Deflazacort is a relatively new glucocorticoid with significant immunosuppressant activity and presumably fewer side effects. The present study was designed to compare the effects of deflazacort on the proliferative activity of thymus cells and thymolysis with the growth inhibition. We treated Long-Evans rats for nine days with cortisone (CORT, 5.0 mg/day), deflazacort (DFZ, 0.15 mg/day), and control vehicle (CTRL). Animals were sacrificed 1 hour after injection of bromodeoxyuridine (BrdUrd) on day 10. BrdUrd-labeled thymic cells were quantified without knowledge of treatment. A Labeling Index (LI), expressed as the number of BrdUrd BrdUrd-labeled cells per 100 total cells and the Numerical Density (ND), expressed as the total number of cells per 100 microm(2) were calculated. Treatment with either glucocorticoid resulted in a significant and equal decrease of thymus weight, indicating a marked reduction in total immunogenic tissue. A general alteration of thymic histological structure occurred in the CORT group. The LI was not different between CTRL and DFZ groups, 6.9 and 7.9% of cells were labeled respectively. In the CORT group, the LI was 2.5%. With respect to Numerical Density, the CTRL group had the greatest value (14.6 +/- 0.4 cells/100 microm(2)), with the DFZ (12.3 +/- 0.06 cells/100 microm(2)) and CORT groups being significantly lower (10.4 +/- 0.5 cells/100 microm(2)). Although regression analysis of thymus weight pointed to bioequivalence of the glucocorticoid dosages used, BrdUrd-labeling raised the possibility that the cells still present in the thymus of DFZ-treated animals retained, at least partially, their normal capacities for proliferation.
Latta
Kay
K
Department of Pediatrics, Medical College of Virginia, Richmond, VA, USA. KayLatta@web.de
Krieg
Richard J
RJ
Carbajo-Pérez
Eduardo
E
Carbajo
Santiago
S
Chan
James C M
JC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000963:Antimetabolites / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D003348:Cortisone / Q000494:pharmacology*; D006651:Histocytochemistry; D009929:Organ Size / Q000187:drug effects; D011282:Pregnenediones / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D016196:S Phase / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000963:Antimetabolites; D011282:Pregnenediones; D001973:Bromodeoxyuridine; C021988:deflazacort; D003348:Cortisone