Improvement of lipoprotein functions related to cell cholesterol trafficking in rheumatoid arthritis patients treated with tocilizumab

Background/Objectives: Rheumatoid Arthritis (RA) is associated with accelerated atherosclerosis, partly attributed to disturbances in serum lipoprotein functions. Tocilizumab treatment, targeting IL-6, is increasingly being used in RA, but with some concern for its effect on serum lipid profile, particularly on high density lipoproteins (HDL). However, as HDL function seems more important than concentration, we evaluated serum HDL capacity to promote cell cholesterol efflux (CEC), known to inversely correlate with cardiovascular risk, in RA patients before and after tocilizumab treatment. Design/Method: serum was drawn from 8 patients with RA before (t0) and after 4 (t1) and 12 (t2) weeks of intravenous treatment (8 mg/Kg/4 weeks). CEC was measured with radioisotopic technique and specific cell models to measure cholesterol efflux through the membrane transporters Scavenger receptor Class B type I (SR-BI) and ATP binding cassette A1 and G1 (ABCA1 and ABCG1), to explore functionality of the various HDL subfractions. Results: SR-BI-mediated CEC increased significantly after treatment (mean±SEM 2.43±0.33, 2.88±0.30, 3.41±0.35 at t0, t1 and t3 respectively; p=0.025 t0 vs t1, p=0.008 t0 vs t3) with unmodified total HDL serum levels, so the ratio SR-BI-mediated CEC/HDL levels increased significantly (p<0.05 t0 vs t3). The same trend, very close to statistical significance (3.97±0.33, 4.44±0.57, 4.97±0.26 at t0, t1 and t3 respectively; p=0.064 t0 vs t3), was observed for ABCG1-mediated CEC. No modification was detected in ABCA1-mediated CEC. After treatment an inverse relationship between SR-BI-mediated CEC and ESR appeared. Conclusions: tocilizumab may have an anti-atherogenic effect improving HDL function, known to be impaired in RA.