Bromocriptine microcapsules inhibit ornithine decarboxylase activity induced by Freund's complete adjuvant in lymphoid tissues of male rats.
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 immuno-stimulatory mechanism, probably involved in the pathogenesis of adjuvant arthritis.
Neidhart
M
M
Preclinical Research Department, Sandoz Ltd., Basel, Switzerland.
D000818:Animals; D001168:Arthritis / Q000201:enzymology*; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000276:immunology; D001853:Bone Marrow / Q000201:enzymology; D001971:Bromocriptine / Q000008:administration & dosage / Q000494:pharmacology*; D002214:Capsules; D002940:Circadian Rhythm; D005620:Freund's Adjuvant; D007700:Kinetics; D008198:Lymph Nodes / Q000201:enzymology; D008221:Lymphoid Tissue / Q000201:enzymology*; D008297:Male; D065108:Ornithine Decarboxylase Inhibitors; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000201:enzymology; D013950:Thymus Gland / Q000201:enzymology
D002214:Capsules; D065108:Ornithine Decarboxylase Inhibitors; D001971:Bromocriptine; D011388:Prolactin; D005620:Freund's Adjuvant