The correlation of cytokine levels with body weight after megestrol acetate treatment in geriatric patients

Background. Cachexia is associated with elevated levels of cytokines in can cer and human immunodeficiency virus patients. Studies in cancer and acquir ed immunodeficiency syndrome patients showed that treatment with megestrol acetate (MA) is associated with improvement in appetite and weight gain. Re duction in the levels of cytokines is associated with weight gain in labora tory animals with cancer. This study evaluates the correlation between chan ges in cytokine (or their receptor) levels and weight following MA treatmen t in geriatric weight-Toss patients. Methods, Veterans Administration Medical Center nursing home patients (N = 69) with a weight loss of greater than or equal to5% of usual body weight o ver the past 3 months or body weight 20% below their ideal body weight part icipated in a 12-week. randomized, double-blind, placebo-controlled trial, with an additional 13-week follow-up period. Patients were randomly assigne d to receive a placebo or MA oral suspension of 800 mg/d for 12 weeks. Leve ls of the following cytokines (DT their receptors) were measured at baselin e and after 12 weeks of treatment: tumor necrosis factor soluble receptor ( TNFR) subunits,TNFR-p55 and TNFR-p75; interleukin 6 (IL-6); and the soluble interleukin-2 receptor (sIL-2R). The subjects' weight and body composition were measured at the start of the study. Weight and mortality were followe d up tor another 13 weeks after discontinuing the MA study drug. Results, Elevated levels of IL-6 in almost all geriatric cachexic patients, compared with normal volunteers (mean, <4.6 pg/ml), were noted at baseline . At 12 weeks after the study drug treatment, there was a decrease in cytok ine levels cor their receptors) in the MA group (mean change in IL-6, -3.63 +/- 6.62 pg/ml; TNFR-p55, -0.06 +/- 0.11 ng/ml; TNFR-p75, -0.01 +/- 0.29 n g/ml; and slL-2R, 0.08 +/- 0.07 ng/ml) and the placebo group (mean change i n IL-6, - 2.08 +/- 3.92 pg/ml: TNFR-p55. -0.02 +/- 0.08 ng/ml; TNFR-p75, -0 .20 +/- 0.18 ng/ml: and slL-2R, 0.02 +/- 0.03 ng/ml). Although the change i n cytokine levels was not statistically significant between the two groups, significant negative correlation (p<0.05) was found. For example, increase d weight correlated with decreased sIL-2R levels (r = -.36) and TNFR-p75 (r = -.31:fat-free mass (FFM) gain and reduction of sIL-2R (r = -.39), TNFR-p 75 (r = -.30). There was a significant correlation between weight gain and reduction of TNFR-p75 (, = -.54), TNFR-p55 (r = -.47), and sIL-2R ( r =-.53 ): FFM gain and reduction of sIL-2R (r- = -.59), TNFR-p75 (r = -.41), TNFR- p55 (r = and reduction of TNFR-p75 (r = -.41) in the MA group (p <.05), but not in the placebo group. Conclusions. Although there was no significant change in cytokine levels be tween the two groups, the reduction in cytokine levels after MNA treatment correlated with improvement in weight, fat mass, and FFM at 12 weeks.