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Bromocriptine Microcapsules Inhibit Ornithine Decarboxylase Activity Induced by Freund's Complete Adjuvant in Lymphoid Tissues of Male Rats

Preclinical Research Department, Sandoz Ltd Basel, Switzerland

Address all correspondence and requests for reprints to: Dr. Michel Neidhart, University of Zurich, Clinic for Rheumatology and Physical Therapy, Gloriastrasse 25, CH-8091 Zurich, Switzerland

Abstract

Arthritis is produced in male rats within 9–10 days after a single injection of Freund's complete adjuvant (FCA) at the base of the tail. When bromocriptine, a dopaminomimetic that suppresses PRL secretion, was given in form of long-acting microcapsules (CBLA) 3 days before FCA, the hind limb swelling was significantly reduced by 70%. Here, we showed that plasma PRL levels were significantly elevated (by 150% over controls) during the 6-day period after FCA, particularly at night. Further, within 1–4 days after FCA inoculation, marked increases in ornithine decarboxylase (ODC) activity occurred in bone marrow, thymus, spleen, and lymph nodes (by 190%, 160%, 80% and 75% over control values, respectively). In FCA-treated rats, the circadian rhythm of thymic ODC showed that an important enhancement of activity occurred during the dark phase, which correlated with the peak of PRL secretion (between 2200–0400 h). Finally, pretreatment with CBLA significantly inhibited the induction of ODC in response to FCA in thymus, spleen, and lymph nodes (by 65%, 80%, and 45%, respectively) and inhibited it more weakly in the bone marrow. This in vivo study leaves little doubt about the existence of a PRL-dependent immunostimulatory mechanism, probably involved in the pathogenesis of adjuvant arthritis.

Received March 30, 1989.

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