Abstract 64: Interleukin-10 Decreases HDL: A Novel Cause of Disappearing HDL Syndrome
Introduction “Disappearing HDL Syndrome” refers to cases of acquired severe HDL deficiency in non-critically ill patients. Except for rare idiosyncratic drug reactions, the physiological basis of Disappearing HDL Syndrome is not understood.
Hypothesis “Disappearing HDL” in patients with B-cell disorders may be due to increased levels of cytokines, particularly IL-10, in plasma.
Methods We investigated cytokine levels in a patient with intravascular large B-cell lymphoma (IVLBCL) who presented with undetectable or very low HDL-C, low LDL-C and markedly elevated triglycerides. IL-10 levels were investigated in additional patients with B-cell disorders (IVLBCL, large B-cell lymphoma, and ALPS) who presented with similar lipid profiles. A direct causal role for IL-10 in modulating HDL-C was investigated with a randomized, placebo-controlled study of recombinant IL-10 infusion into psoriatic arthritis patients.
Results All cases (IVLBCL, large B-cell lymphoma and ALPS) had highly elevated serum IL-10 levels that normalized after chemotherapy concomitant with normalization of HDL-C, LDL-C and TG. In a survey of 93 ALPS patients, IL-10 showed a strong inverse correlation with HDL-C (R2 = 0.3720, p<0.0001). In a randomized, placebo-controlled study of recombinant IL-10 infusion into psoriatic arthritis patients HDL-C precipitously decreased to near-undetectable levels shortly after IL-10 injection. Furthermore, IL-10 treatment also decreased LDL-C by 51% or more during IL-10 administration (p < 0.005) and increased TG by up to 2-fold.
Conclusions Our study has identified increased IL10 as a potential cause of Disappearing HDL Syndrome and demonstrated that in addition to HDL-C, IL-10 can also modulated levels of LDL-C and TG, thus identifying a new link between inflammation and lipid metabolism.
- © 2013 by American Heart Association, Inc.