Effect of iguratimod and other anti-rheumatic drugs on adenocarcinoma colon 26-induced cachexia in mice

Objective: To examine the effect of iguratimod (T-614) and other anti-rheumatic drugs on a mouse model of adenocarcinoma-induced cachexia. Methods: Cachexia was induced in BALB/c mice by s. c. inoculation of colon 26/clone 20 cells (day 0). The drugs were administered p. o. daily from day 0 for 15 days for prophylactic experiments and from day 7 for 8 days for therapeutic experiments. Serum biochemical parameters and wasting of adipose tissue and muscle were evaluated as the nutritional condition in tumor-bearing mice at day 14. Interleukin-6 (IL-6) levels in serum and tumor tissue of those mice were also quantified. Results: Administration of T-614 did not inhibit the tumor growth, but it resulted in attenuation of cachexia symptoms, such as the reduction in epididymal fat and gastrocnemius muscle, and the decrease of serum albumin. Furthermore, T-614 decreased the serum levels of IL-6, and reduced its gene expression in the tumor tissues. Exogenously administered IL-6 nullified the suppressive effect of T-614. Prednisolone prevented the weight loss and the wasting without inhibiting tumor growth. Methotrexate and indomethacin did not exert any preferable effects in a therapeutic dosing schedule. Conclusions: Our results demonstrate that T-614 exerts an anticachectic effect in tumor-bearing mice through the inhibition of IL-6 gene expression. Received 3 February 2006; returned for revision 9 April 2006; returned for final revision 5 June 2006; accepted by M. Katori 24 July 2006