Systemic α-melanocyte-stimulating hormone administration decreases arthritis-induced anorexia and muscle wasting

Rheumatoid cachexia is associated with rheumatoid arthritis and it increases mortality and morbidity. Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that causes anorexia and muscle wasting. alpha-Melanocyte-stimulating hormone (alpha-MSH) has anti-inflammatory actions, and it is able to decrease inflammation in several inflammatory diseases including experimental arthritis. In this study we tested whether systemic alpha-MSH treatment is able to ameliorate cachexia in arthritic rats. On day 8 after adjuvant injection control and arthritic rats were treated with alpha-MSH (50 mu g/rat ip) twice a day, until day 16 when all rats were euthanized. Arthritis decreased food intake, but it increased hypothalamic expression of neuropeptide Y (NPY) and Agouti-related peptides (AgRP) as well as interleukin-1 beta (IL-1 beta) and cyclooxygenase-2 (COX-2) mRNA. In arthritic rats, alpha-MSH decreased the external signs of arthritis and increased food intake (P < 0.01). In addition, alpha-MSH decreased hypothalamic expression of IL-1 beta, COX-2, proopiomelanocortin, and prohormone-converting (PC) enzymes PC1/3 and PC2 mRNA in arthritic rats. In control rats, alpha-MSH did not modify food intake or hypothalamic expression of aforementioned mRNA. alpha-MSH prevented arthritis-induced increase in gastrocnemius COX-2, muscle-specific RING-finger protein-1 (MuRF1), and atrogin-1 expression, and it increased fast myofiber size. In conclusion our data show that in arthritic rats peripheral alpha-MSH treatment has an anti-cachectic action increasing food intake and decreasing muscle wasting.