title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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: Metabolism, Endocrinology & Diabetes, Endocrine Oncology Program, University of Michigan, Ann Arbor, MI, USA.
authors: Andreas G
authors: AG
authors: Moraitis
authors: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Lita A
authors: LA
authors: Freeman
authors: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Robert D
authors: RD
authors: Shamburek
authors: Hospital Epidemiology, National Institutes of Health, Bethesda, MD, USA.
authors: Robert
authors: R
authors: Wesley
authors: National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Wyndham
authors: W
authors: Wilson
authors: National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Cliona M
authors: CM
authors: Grant
authors: ALPS Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Susan
authors: S
authors: Price
authors: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Stephen
authors: S
authors: Demosky
authors: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Seth G
authors: SG
authors: Thacker
authors: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Abdalrahman
authors: A
authors: Zarzour
authors: Clinical Services Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors: Ronald L
authors: RL
authors: Hornung
authors: National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Frank
authors: F
authors: Pucino
authors: Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, USA.
authors: Gyorgy
authors: G
authors: Csako
authors: National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Cheryl
authors: C
authors: Yarboro
authors: National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA; College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors: Iain B
authors: IB
authors: McInnes
authors: National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Takashi
authors: T
authors: Kuroiwa
authors: National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA; Medical School University of Athens, Affiliate Member IMBB, Heraklion and BRFAA Athens, Greece.
authors: Dimitrios
authors: D
authors: Boumpas
authors: ALPS Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: V Koneti
authors: VK
authors: Rao
authors: National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Gabor G
authors: GG
authors: Illei
authors: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, USA. Electronic address: aremaley1@cc.nih.gov.
authors: Alan T
authors: AT
authors: Remaley
mesh_terms: D000328:Adult; D015535:Arthritis, Psoriatic / Q000188:drug therapy; D056735:Autoimmune Lymphoproliferative Syndrome / Q000097:blood / Q000175:diagnosis; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000175:diagnosis; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D019014:fas Receptor / Q000235:genetics
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C491901:FAS protein, human; D011994:Recombinant Proteins; D014280:Triglycerides; D019014:fas Receptor; D016753:Interleukin-10
keywords: ALPS; B-cell lymphoma; Dyslipidemia; Hypertriglyceridemia; IL-10; Intravascular large B-cell lymphoma; LCAT; Psoriasis; Severe HDL deficiency; “Disappearing HDL syndrome”