EVALUATION OF A MODEL FOR POSTPARTUM ARTHRITIS AND THE ROLE OF ESTROGEN IN PREVENTION OF MRL-LPR ASSOCIATED RHEUMATIC CONDITIONS

Sixty-eight percent of female MRL-lpr mice developed a post-partum exa cerbation of their mild spontaneous arthritis within 30 days of partur ition. The flare became evident between 5 and 15 days after delivery. Histologically it was characterized by a significant increase of subsy novial inflammation and synovial hyperplasia without changes in the le vel of cartilage and bone erosion. Immunohistologically, marked subsyn ovial and frequent synovial staining of MHC class II bearing cells was noted, along with the sporadic presence of CD3, CD4, and CD43 recepto r-bearing cells in the subsynovium. Injection of physiological levels (0.08 mg/kg) of estradiol on days 2, 3, 9, 15 and 20 post-partum delay ed and reduced the flare to 23% of the animals. Administration of phar macological amounts (0.4 mg/kg per day for 2 weeks following Freund's complete adjuvant injection) prevented adjuvant-enhanced arthritis, re ducing the incidence from 67% to the baseline 21% level. Deleterious c hanges in the underlying systemic lupus erythematosus (SLE), as demons trated by proteinurea and mortality rate increases, were elicited only by the employed pharmacological amounts of estradiol. These results i ndicate that the MRL-lpr mice might serve as a model for post-partum f lare of arthritis in SLE and rheumatoid arthritis by providing an appr oach to study the complexity of the effects of pregnancy on autoimmune diseases, and to obtain further evidence for the involvement of oestr ogen in arthritis.