Lipid metabolism derangement contributes to increased cardiovascular risk in Rheumatoid Arthritis (RA). It is still debated whether and how tocilizumab, an interleukin-6 receptor inhibitor used in active RA, impacts cardiovascular risk. We studied the effect of tocilizumab on the regulation of macrophage cholesterol homeostasis, measuring patient serum ability to respectively load (cholesterol loading capacity, CLC) and discharge (cholesterol efflux capacity, CEC) cells with cholesterol. Patients with RA (n = 8) were studied before and after 4 and 12 weeks of tocilizumab treatment. CLC was measured by a fluorimetric assay of intracellular cholesterol content in human macrophages and CEC was measured for the three main pathways, mediated by the transporters Scavenger Receptor class B-type I (SR-BI), ATP binding cassette-G1 (ABCG1) and -A1 (ABCA1) in specific cell models. After 12 weeks of tocilizumab treatment, serum LDL cholesterol levels were increased, while CLC was reduced. HDL cholesterol levels were unchanged, but CEC was significantly ameliorated for the SR-BI and ABCG1 pathways with respect to baseline. Tocilizumab reduces LDL pro-atherogenic potential despite increasing their serum levels and increases HDL protective activity in RA. The data of our pilot study suggest that tocilizumab regulates lipoprotein function in selected patient populations and lay the groundwork for future larger studies.

Anti-atherogenic Modification of Serum Lipoprotein Function in Patients with Rheumatoid Arthritis after Tocilizumab Treatment, a Pilot Study / D. Greco, R. Gualtierotti, P. Agosti, M.P. Adorni, F. Ingegnoli, M. Rota, F. Bernini, P.L. Meroni, N. Ronda. - In: JOURNAL OF CLINICAL MEDICINE. - ISSN 2077-0383. - 9:7(2020 Jul 08). [10.3390/jcm9072157]

Anti-atherogenic Modification of Serum Lipoprotein Function in Patients with Rheumatoid Arthritis after Tocilizumab Treatment, a Pilot Study

R. Gualtierotti
Secondo
;
P. Agosti;F. Ingegnoli;M. Rota;P.L. Meroni
Penultimo
;
2020-07-08

Abstract

Lipid metabolism derangement contributes to increased cardiovascular risk in Rheumatoid Arthritis (RA). It is still debated whether and how tocilizumab, an interleukin-6 receptor inhibitor used in active RA, impacts cardiovascular risk. We studied the effect of tocilizumab on the regulation of macrophage cholesterol homeostasis, measuring patient serum ability to respectively load (cholesterol loading capacity, CLC) and discharge (cholesterol efflux capacity, CEC) cells with cholesterol. Patients with RA (n = 8) were studied before and after 4 and 12 weeks of tocilizumab treatment. CLC was measured by a fluorimetric assay of intracellular cholesterol content in human macrophages and CEC was measured for the three main pathways, mediated by the transporters Scavenger Receptor class B-type I (SR-BI), ATP binding cassette-G1 (ABCG1) and -A1 (ABCA1) in specific cell models. After 12 weeks of tocilizumab treatment, serum LDL cholesterol levels were increased, while CLC was reduced. HDL cholesterol levels were unchanged, but CEC was significantly ameliorated for the SR-BI and ABCG1 pathways with respect to baseline. Tocilizumab reduces LDL pro-atherogenic potential despite increasing their serum levels and increases HDL protective activity in RA. The data of our pilot study suggest that tocilizumab regulates lipoprotein function in selected patient populations and lay the groundwork for future larger studies.
atherosclerosis; cardiovascular disease; cellular cholesterol; cholesterol efflux; cholesterol loading; lipoproteins; macrophages; rheumatoid arthritis; tocilizumab
Settore MED/09 - Medicina Interna
Settore MED/16 - Reumatologia
Translational medicine between clinical practice and research: dissecting immunological mechanisms of rheumatoid arthritis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/785103
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