Evidence for a Link Between Adipose Tissue Interleukin-6 Content and Serum C-Reactive Protein Concentrations in Obese Subjects
To the Editor:
We read with interest the editorial by Tracy1 on inflammation in cardiovascular disease (CVD). Serum concentrations of C-reactive protein (CRP) were demonstrated to be related to increased risk of CVD, which underlines the potential inflammatory nature of human atherosclerosis.2 3 Interestingly, an unexpected association between CRP and body mass index (BMI) was found in several population studies2 3 4 without any explanation.1
The production of CRP is regulated by cytokines, principally interleukin-6 (IL-6), and serum CRP levels reflect IL-6 activity in humans. It was demonstrated that IL-6 is released in vivo by subcutaneous adipose tissue and is thereby able to have systemic effects, particularly in obese subjects.5 Thus, we hypothesized that adipose tissue may play a role in the regulation of serum CRP concentrations via IL-6 production.
To test this hypothesis, we measured CRP and IL-6 in both blood and adipose tissue from 13 fasting obese subjects (2 men, 11 women) aged 44±4 years (BMI, 39.1±1.3 kg/m2; percent fat mass, 44.3±2.4%). CRP concentrations were determined with a BNII nephelometer analyser (Behring). IL-6 concentrations were determined by ELISA (Quantikine, R&D Systems). Body composition analysis was carried out by dual x-ray absorptiometry (QDR 1000, Hologic).
Serum CRP and IL-6 concentrations were 4.49±1.07 mg/L and 2.77±0.31 pg/mL, respectively. In adipose tissue, IL-6 concentrations were 12.81±1.28 pg/g fat, whereas CRP was undetectable. Serum CRP concentrations were significantly correlated with BMI (ρ=0.633, P<0.05), body fat mass (ρ=0.718, P<0.05), and percent fat mass (ρ=0.872, P<0.005) but not with lean body mass (ρ=−0.435, P=0.13). A strong correlation was found between serum CRP concentrations and adipose tissue IL-6 content when expressed as picogram per total fat mass (ρ=0.757, P<0.01) but not as picogram per gram of fat (ρ=0.446, P=0.12).
These data are consistent with the role of human adipose tissue in the regulation of blood circulating CRP concentrations via IL-6 production in obesity. In addition, the higher IL-6 production from adipose tissue seems to be more related to the increase of total fat mass than an overexpression of IL-6 in adipose tissue. Because CRP was proposed as a predictive marker of CVD risk, whether slightly elevated concentrations of CRP are the consequence of adipose tissue secretion, an inflammatory process, or both remains to be established.
- Copyright © 1999 by American Heart Association
Tracy RP. Inflammation in cardiovascular disease: cart, horse, or both? Circulation. 1998;97:2000–2002.
Mendall MA, Patel P, Ballam L, Strachan D, Northfield TC. C-reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ. 1996;312:1061–1065.
Tracy RP, Psaty BM, Macy E, Bovill EG, Cushman M, Cornell ES, Kuller LH. Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects. Arterioscler Thromb Vasc Biol. 1997;17:2167–2176.