title: Lipid-heparin infusion suppresses the IL-10 response to trauma in subcutaneous adipose tissue in humans.
abstract: An imbalance between pro- and anti-inflammatory cytokine productions in adipose tissue is thought to contribute to chronic, systemic, low-grade inflammation and consequently to an increased risk of cardiovascular complications in obese and type 2 diabetic patients. Nonesterified fatty acids (NEFA), whose serum levels are elevated in such patients, have been shown to interfere with cytokine production in vitro. In order to evaluate the effects of elevated NEFA levels on cytokine production in adipose tissue in vivo we used an 18-gauge open-flow microperfusion (OFM) catheter to induce local inflammation in the subcutaneous adipose tissue (SAT) of healthy volunteers and to sample interstitial fluid (IF) specifically from the inflamed tissue. In two crossover studies, nine subjects received either an intravenous lipid-heparin infusion to elevate circulating NEFA levels or saline over a period of 28 h. The former increased the circulating levels of triglycerides (TGs), NEFA, glucose, and insulin over the study period. NEFA effects on locally induced inflammation were estimated by measuring the levels of a panel adipokines in the OFM probe effluent. Interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) levels increased during the study period but were not affected by lipid-heparin infusion. In contrast, the level of IL-10, an anti-inflammatory cytokine, was significantly reduced during the final hour of lipid-heparin infusion (saline: 449.2 ± 105.9 vs. lipid-heparin: 65.4 ± 15.4 pg/ml; P = 0.02). These data provide the first in vivo evidence that elevated NEFA can modulate cytokine production by adipose tissue.
authors.affiliation: Department of Internal Medicine, Medical University of Graz, Graz, Austria. dimas.ikeoka@healthsite.at
authors.forename: Dimas T
authors.initials: DT
authors.lastname: Ikeoka
authors.forename: Christoph
authors.initials: C
authors.lastname: Pachler
authors.forename: Julia K
authors.initials: JK
authors.lastname: Mader
authors.forename: Gerlies
authors.initials: G
authors.lastname: Bock
authors.forename: Ana L
authors.initials: AL
authors.lastname: Neves
authors.forename: Eva
authors.initials: E
authors.lastname: Svehlikova
authors.forename: Franz
authors.initials: F
authors.lastname: Feichtner
authors.forename: Gerd
authors.initials: G
authors.lastname: Koehler
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wrighton
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.forename: Martin
authors.initials: M
authors.lastname: Ellmerer
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D057785:Catheters; D018932:Chemokine CCL2 / Q000097:blood; D018592:Cross-Over Studies; D016207:Cytokines / Q000096:biosynthesis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage* / Q000097:blood; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007328:Insulin / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000150:complications / Q000276:immunology; D012189:Retrospective Studies; D050151:Subcutaneous Fat / Q000378:metabolism* / Q000503:physiopathology; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D054392:Adipokines; D001786:Blood Glucose; C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; C508609:IL10 protein, human; C508600:IL6 protein, human; D007328:Insulin; D015850:Interleukin-6; D016209:Interleukin-8; D008055:Lipids; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D006493:Heparin