Impaired mononuclear cell immune function in extreme obesity is corrected by weight loss.
BACKGROUND
Obesity is associated with an increased prevalence and severity of infections. The mechanism(s) responsible for the increased risk of infections is unclear. We evaluated the effects of excessive adiposity and weight loss on peripheral blood mononuclear cell (PBMC) chemokine (macrophage chemoattractant protein-1 [MCP-1) and cytokine (interferon-gamma [IFNgamma]) production, which is an important component of the immune response to infectious pathogens.


METHODS
Lipopolysaccharide (LPS)and phorbol 12-myristate 13-acetate plus ionomycin (PMA + I)-stimulated PBMC MCP-1 and IFNgamma production were determined in six extremely obese subjects (body mass index [BMI] = 62.4 +/- 8.6 kg/m(2)) before and 1 year after gastric bypass surgery and in six age-matched lean subjects (BMI = 22.7 +/- 1.4 kg/m(2)).


RESULTS
At baseline, LPS-stimulated MCP-1 production and PMAI-stimulated IFNgamma production by PBMCs were 93.6% +/- 4.9% and 88.8% +/- 9.6% lower, respectively, in obese than in lean subjects (p < 0.03). Obese subjects lost 30.3% +/- 10.6% of their body weight at 1 year after gastric bypass surgery (p < 0.001). Weight loss completely restored LPS-stimulated MCP-1 production and PMA+I-stimulated IFNgamma production in obese subjects to normal.


CONCLUSIONS
Agonist-stimulated production of IFNgamma and MCP-1 are markedly suppressed in subjects with extreme obesity. Weight loss completely normalizes the ability of stimulated PBMCs to produce MCP-1 and IFNgamma. These findings could have important implications in understanding the increased risk of infections associated with obesity, and demonstrate a unique beneficial effect of weight loss on immune function.
Fontana
Luigi
L
Division of Geriatrics and Nutritional Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA. lfontana@im.wustl.edu
Eagon
J Christopher
JC
Colonna
Marco
M
Klein
Samuel
S
D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D009767:Obesity, Morbid / Q000276:immunology* / Q000628:therapy*; D015431:Weight Loss