Antiarthritic Effects of Relaxin, in Combination with Estrogen, in Rat Adjuvant-Induced Arthritis

• Published in: The Journal of pharmacology and experimental therapeutics 2007-08, Vol.322 (2), p.887-893
• Main Authors: Santora, Karen, Rasa, Cordelia, Visco, Denise, Steinetz, Bernard G, Bagnell, Carol A
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - toxicity; Animals; Arthritis, Experimental - blood; Arthritis, Experimental - chemically induced; Arthritis, Experimental - drug therapy; Body Weight - drug effects; Drug Therapy, Combination; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estradiol - therapeutic use; Estrogen Antagonists - pharmacology; Estrogen Antagonists - therapeutic use; Estrogens - pharmacology; Estrogens - therapeutic use; Female; Hindlimb; Inflammation - chemically induced; Inflammation - drug therapy; Interleukin-10 - blood; Mycobacterium - chemistry; Mycobacterium - immunology; Organ Size - drug effects; Ovariectomy; Pregnancy; Rats; Rats, Inbred Lew; Relaxin - pharmacology; Relaxin - therapeutic use; Spleen - pathology; Swine; Thymus Gland - pathology; Tumor Necrosis Factor-alpha - blood; Vascular Endothelial Growth Factor A - blood
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.107.122903

The incidence and severity of rheumatoid arthritis (RA) are reduced during pregnancy. Estradiol-17β and relaxin (RLX), hormones of pregnancy, are implicated in decreased immune responsiveness. The aim of this study was to determine the effects of estrogen and RLX, alone or in combination, on the development of adjuvant-induced arthritis (AIA) in ovariectomized (OVX) Lewis rats. Arthritis was induced on day 0 by adjuvant injection in the left hind paw. Rats were treated with estradiol valerate (E), porcine RLX, E + RLX, or vehicle. Healthy OVX control animals were used for comparison. Treatment with RLX or E alone decreased adjuvant-induced inflammation in both the injected (primary) and noninjected (secondary) hind paws. Combined treatment with E and RLX was more effective than either hormone alone in blocking secondary paw inflammation. Furthermore, E plus RLX reduced changes to spleen and thymus weights induced by adjuvant injection. Both E and RLX alone decreased circulating tumor necrosis factor (TNF) α. The combination of E and RLX resulted in a greater decline in TNFα than treatment with either hormone alone. There was no effect of hormones on the proinflammatory cytokine, interleukin (IL)-1β. The anti-inflammatory cytokine IL-10 increased in response to E and E plus RLX. In conclusion, combined therapy with E and RLX was more effective than either hormone alone in reducing chronic inflammation, joint changes, and high circulating TNFα associated with AIA in rats. Accordingly, these hormones could play a role in reducing RA-induced inflammation during pregnancy by an effect on the immune system.