TY - JOUR
TI - Elevated interleukin-10: A new cause of dyslipidemia leading to severe
HDL deficiency
AU - Moraitis, Andreas G.
AU - Freeman, Lita A.
AU - Shamburek, Robert D. and
AU - Wesley, Robert
AU - Wilson, Wyndham
AU - Grant, Cliona M.
AU - Price, Susan
AU - and Demosky, Stephen
AU - Thacker, Seth G.
AU - Zarzour, Abdalrahman and
AU - Hornung, Ronald L.
AU - Pucino, Frank
AU - Csako, Gyorgy
AU - Yarboro,
AU - Cheryl
AU - McInnes, Iain B.
AU - Kuroiwa, Takashi
AU - Boumpas, Dimitrios
AU - and Rao, V. Koneti
AU - Illei, Gabor G.
AU - Remaley, Alan T.
JO - Journal of Clinical Lipidology
PY - 2015
VL - 9
TODO - 1
SP - 81-90
PB - EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
SN - 1933-2874
TODO - 10.1016/j.jacl.2014.09.014
TODO - “Disappearing HDL syndrome”; Severe HDL deficiency;
Hypertriglyceridemia; Dyslipidemia; B-cell lymphoma; Intravascular large
B-cell lymphoma; ALPS; Psoriasis; IL-10; LCAT
TODO - 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.
ER -