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

Autor: Moraitis, Andreas G. Freeman, Lita A. Shamburek, Robert D. and Wesley, Robert Wilson, Wyndham Grant, Cliona M. Price, Susan and Demosky, Stephen Thacker, Seth G. Zarzour, Abdalrahman and Hornung, Ronald L. Pucino, Frank Csako, Gyorgy Yarboro, Cheryl McInnes, Iain B. Kuroiwa, Takashi Boumpas, Dimitrios and Rao, V. Koneti Illei, Gabor G. Remaley, Alan T.
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Popis: BACKGROUND: 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 EIDL syndrome”) could provide new insights into HDL metabolism. OBJECTIVE: To determine the cause of low HDL-C in patients with severe acquired HDL deficiency. METHODS AND RESULTS: 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 EIDL-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. CONCLUSION: 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. Published by Elsevier Inc. on behalf of National Lipid Association.
Databáze: OpenAIRE