Decreasing levels of tumour necrosis factor alpha and interleukin 6 during lowering of body mass index with orlistat or placebo in obese subjects with cardiovascular risk factors.
OBJECTIVE
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) F2alpha during BMI lowering with orlistat (Xenical(R), Roche) or placebo.


METHODS
TNF-alpha, IL-6, and 8-epi PGF2alpha evaluated in 376 subjects aged 18-75 years with BMI 28-38 kg/m2 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-PGF2alpha correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001).


CONCLUSIONS
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.
Samuelsson
L
L
Department of Vascular Diseases, University Hospital, S-205 02 Malmö, Sweden.
Gottsäter
A
A
Lindgärde
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D007783:Lactones / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000077403:Orlistat; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015431:Weight Loss
D019440:Anti-Obesity Agents; D015850:Interleukin-6; D007783:Lactones; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; C075750:8-epi-prostaglandin F2alpha; D000077403:Orlistat; D015237:Dinoprost