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Elevated interleukin-10: a new cause of dyslipidemia leading to severe HDL deficiency.

Journal of clinical lipidology (2015-02-12)
Andreas G Moraitis, Lita A Freeman, Robert D Shamburek, Robert Wesley, Wyndham Wilson, Cliona M Grant, Susan Price, Stephen Demosky, Seth G Thacker, Abdalrahman Zarzour, Ronald L Hornung, Frank Pucino, Gyorgy Csako, Cheryl Yarboro, Iain B McInnes, Takashi Kuroiwa, Dimitrios Boumpas, V Koneti Rao, Gabor G Illei, Alan T Remaley
ABSTRACT

Low high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. Investigating mechanisms underlying acquired severe HDL deficiency in noncritically ill patients ("disappearing HDL syndrome") could provide new insights into HDL metabolism. To determine the cause of low HDL-C in patients with severe acquired HDL deficiency. Patients with intravascular large B-cell lymphoma (n = 2), diffuse large B-cell lymphoma (n = 1), and autoimmune lymphoproliferative syndrome (n = 1) presenting with markedly decreased HDL-C, low low-density lipoprotein cholesterol (LDL-C), and elevated triglycerides were identified. The abnormal lipoprotein profile returned to normal after therapy in all 4 patients. All patients were found to have markedly elevated serum interleukin-10 (IL-10) levels that also normalized after therapy. In a cohort of autoimmune lymphoproliferative syndrome patients (n = 93), IL-10 showed a strong inverse correlation with HDL-C (R(2) = 0.3720, P < .0001). A direct causal role for increased serum IL-10 in inducing the observed changes in lipoproteins was established in a randomized, placebo-controlled clinical trial of recombinant human IL-10 in psoriatic arthritis patients (n = 18). Within a week of initiating subcutaneous recombinant human IL-10 injections, HDL-C precipitously decreased to near-undetectable levels. LDL-C also decreased by more than 50% (P < .0001) and triglycerides increased by approximately 2-fold (P < .005). All values returned to baseline after discontinuing IL-10 therapy. Increased IL-10 causes severe HDL-C deficiency, low LDL-C, and elevated triglycerides. IL-10 is thus a potent modulator of lipoprotein levels, a potential new biomarker for B-cell disorders, and a novel cause of disappearing HDL syndrome.

MATERIALS
Product Number
Brand
Product Description

SAFC
Cholesterol, Plant-Derived, SyntheChol®, NF, Ph. Eur., JP
Sigma-Aldrich
Cholesterol, from sheep wool, ≥92.5% (GC), powder
Sigma-Aldrich
Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
Sigma-Aldrich
Cholesterol, tested according to Ph. Eur.
Supelco
Cholesterol solution, certified reference material, 10 mg/mL in chloroform
Sigma-Aldrich
Cholesterol, Sigma Grade, ≥99%
SAFC
Cholesterol, from sheep wool, Controlled origin, meets USP/NF testing specifications
Sigma-Aldrich
Cholesterol, Vetec, reagent grade, ≥92.5%
Supelco
Cholesterol, Pharmaceutical Secondary Standard; Certified Reference Material