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

Moraitis, A. G. et al. (2015) Elevated interleukin-10: a new cause of dyslipidemia leading to severe HDL deficiency. Journal of Clinical Lipidology, 9(1), pp. 81-90. (doi:10.1016/j.jacl.2014.09.014) (PMID:25670364)

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Abstract

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 HDL 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 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 (R2 = 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain
Authors: Moraitis, A. G., Freeman, L. A., Shamburek, R. D., Wesley, R., Wilson, W., Grant, C. M., Price, S., Demosky, S., Thacker, S. G., Zarzour, A., Hornung, R. L., Pucino, F., Csako, G., Yarboro, C., McInnes, I. B., Kuroiwa, T., Boumpas, D., Rao, V. K., Illei, G. G., and Remaley, A. T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Clinical Lipidology
Publisher:Elsevier Inc.
ISSN:1933-2874
ISSN (Online):1876-4789

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