Effects of interleukin-2 (IL-2) on human plasma lipid, lipoprotein, and C-reactive protein

Abstract

Six patients with confirmed malignant disease received four consecutive weekly cycles of human recombinant interleukin-2 (IL-2) 4 days/week, continuous iv. infusion, 3 X 10(6) U/m2/day. Plasma cholesterol decreased a mean of 7% within 24 hours after IL-2 infusion and decreased by 33% within 4 days. Plasma cholesterol was significantly lower than baseline concentration by day 21 (-21%), and day 25 (-41%) was significantly lower than day 21. Decreased plasma cholesterol was the result of decreased HDL and LDL cholesterol concentrations. Plasma triglyceride demonstrated a mean increase of 46% after 4 days of therapy and remained greater than baseline concentrations at all time points analyzed. Apolipoprotein AI and AII decreased concomitantly with HDL-cholesterol concentrations, whereas apolipoprotein B after an initial mean decrease of 17% during the first cycle was not significantly different from baseline during the fourth cycle. Apolipoprotein E and Lp(a) were not significantly affected by IL-2 treatment. Plasma C-reactive protein (CRP) increased by 79% within 24 hours of therapy, increased by 254% on day 4, then decreased to baseline concentrations by day 21 after 3 days off of IL-2. Day 25 CRP was elevated compared to both baseline and day 21 concentrations. IL-2 induced plasma lipoprotein changes may be due in part to the induction of interferon gamma.

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

“…LPS, TNF, IL-2, IFN-␤, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor decrease serum cholesterol, whereas IL-1 has no effect (24,25,36,42,(93)(94)(95)(96)(97). The decrease in cholesterol is accompanied by a reduction in serum apoB levels.…”

“…(LIF), ciliary neurotropic factor (CNTF), nerve growth factor (NGF), keratinocyte growth factor (KGF), plateletactivating factor (PAF), and parathyroid hormone-related protein (PTHrP) (30,(32)(33)(34)(35)(36)(37)(38)(39)(41)(42)(43)(44)(45)(46)(47) (Table 1), suggesting redundancy. IL-4, an anti-inflammatory cytokine, opposes the action of some, but not all, of these cytokines (48).…”