SYNERGISM BETWEEN LONG-ACTING BROMOCRYPTINE MICROCAPSULES AND CYCLOSPORINE-A IN THE PREVENTION OF VARIOUS AUTOIMMUNE-DISEASES IN RATS

Pre-treatment of male Sprague-Dawley rats with long-acting bromoerypti ne microcapsules (CBLA) significantly inhibited the arthritic response to Freund's complete adjuvant and reduced weight loss, thymolysis, sp lenomegaly and leukocytosis. In the prevention of adjuvant arthritis ( AA), the combination of CBLA plus sub-optimal doses of cyclosporine A (CsA) was more efficient than either of the drugs alone. Sub-optimal d oses of CsA were 0.1 and 1.0 mg/kg/day s.c. for 5 days. Furthermore, C BLA alone did not decrease the incidence of experimental allergic uvei tis (EAU) in the male Lewis rats. Low-dose CsA reduced the incidence o f uveitis by 50%, and with the addition of CBLA, 100% of rats were pro tected. Low-dose CsA was 2 mg/kg/day i.m. for 14 days. Long-term treat ment of male Sprague-Dawley rats with CBLA alone reduced the incidence and severity of spontaneous autoimmune periarteritis nodosa (PN) in a dose-dependent manner; CsA was less potent than CBLA, and only additi ve effects were obtained. Finally, for the prevention of spontaneous a utoimmune insulin-dependent diabetes (DM), the administration of CBLA did not improve the effect of a low-dose CsA in male BE rats. Neverthe less, a delay in onset of DM could be achieved. A sequential therapy u sing CsA plus CBLA clearly showed beneficial effects. The dose of CsA was 10 mg/kg p.o. 6 days/week for 21 weeks. Compared with Sprague-Dawl ey or Lewis male rats, BE male rats showed only weak prolactin suppres sion after the same doses of CBLA. It is suggested that the use of CBL A may be particularly beneficial in autoimmune disorders. The effectiv eness of the combination therapy CBLA plus CsA, however, was dependent on the model considered. Various factors could play a role: (1) the d ifferent ways of administering CsA (s.c. in AA, i.m. in EAU and PN, or al in DM); (2) strain-dependency in the capacity of CBLA to suppress P rl secretion; and (3) at least in the BE rats, the transient increase of CsA bioavailibility which was possibly induced by CBLA.