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

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 (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.

• Authors: 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
• Journal: Journal of clinical lipidology (J Clin Lipidol) 2015 Jan-Feb Vol. 9 Issue 1 Pg. 81-90 ISSN: 1933-2874 [Print] United States
• PMID: 25670364 (Publication Type: Case Reports, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Cholesterol, HDL
• Cholesterol, LDL
• FAS protein, human
• Recombinant Proteins
• Triglycerides
• fas Receptor
• Interleukin-10

Topics

• Adult
• Arthritis, Psoriatic (drug therapy)
• Autoimmune Lymphoproliferative Syndrome (blood, diagnosis)
• Child
• Cholesterol, HDL (blood)
• Cholesterol, LDL (blood)
• Cohort Studies
• Dyslipidemias (blood, diagnosis)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Infant
• Interleukin-10 (blood, genetics, therapeutic use)
• Lymphoma, B-Cell (diagnosis)
• Lymphoma, Large B-Cell, Diffuse (diagnosis)
• Male
• Middle Aged
• Placebo Effect
• Recombinant Proteins (biosynthesis, genetics, therapeutic use)
• Treatment Outcome
• Triglycerides (blood)
• fas Receptor (genetics)