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Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Impaired mononuclear cell immune function in extreme obesity is corrected by weight loss
Luigi Fontana1, J Christopher Eagon, Marco Colonna
1Division of Geriatrics and Nutritional Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA. lfontana@im.wustl.edu
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.
Insights
Extreme obesity significantly suppresses immune cell production of key signaling molecules. Weight loss reverses this suppression, restoring normal immune function and potentially reducing infection risk.
Area of Science:
- Immunology
- Metabolic Disorders
- Infectious Disease
Background:
- Obesity is linked to increased infection susceptibility and severity.
- Mechanisms underlying obesity-related infection risk remain unclear.
- Immune cell chemokine and cytokine production are crucial for fighting pathogens.
Purpose of the Study:
- To investigate the impact of extreme obesity and subsequent weight loss on immune cell function.
- To assess changes in macrophage chemoattractant protein-1 (MCP-1) and interferon-gamma (IFNgamma) production by peripheral blood mononuclear cells (PBMCs).
Main Methods:
- Compared immune cell function in extremely obese subjects versus lean controls.
- Measured MCP-1 and IFNgamma production by PBMCs stimulated with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate plus ionomycin (PMA + I).
- Evaluated changes in obese subjects one year after gastric bypass surgery.
Main Results:
- Obese subjects exhibited significantly lower LPS-stimulated MCP-1 and PMA+I-stimulated IFNgamma production compared to lean individuals.
- Gastric bypass surgery led to substantial weight loss (30.3%) in obese subjects.
- Weight loss normalized MCP-1 and IFNgamma production by PBMCs in previously obese subjects.
Conclusions:
- Immune cell production of IFNgamma and MCP-1 is markedly suppressed in extreme obesity.
- Weight loss effectively restores normal immune cell function in producing these critical molecules.
- Findings highlight a significant beneficial effect of weight loss on immune function, potentially explaining reduced infection risk in leaner individuals.
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