Decreasing levels of tumour necrosis factor α and interleukin 6 during lowering of body mass index with orlistat or placebo in obese subjects with cardiovascular risk factors

Aim: Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and the isoprostane 8-epi-prostaglandin (PG) F-2alpha during BMI lowering with orlistat (Xenical(R), Roche) or placebo. Methods: TNF-alpha, IL-6, and 8-epi PGF(2alpha) evaluated in 376 subjects aged 18-75 years with BMI 28-38 kg/m(2) before and after 1 year of double-blind, randomized treatment with orlistat 120 mg or placebo three times daily. Results: Weight reduction was associated with decreasing (p < 0.001) levels of TNF-alpha and IL-6 in both orlistat and placebo groups. After 12 months, TNF-alpha was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF-alpha correlated with change in s-glucose (r = 0.22; p = 0.01), and the change in 8-epi-PGF(2alpha) correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001). Conclusion: Weight reduction was associated with decreasing levels of both TNF-alpha and IL-6. After 12 months of treatment, TNF-alpha levels were lower in orlistat than in placebo-treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.