Background/Purpose: The increased risk of major adverse cardiovascular events (MACE) in patients who suffer from systemic inflammatory conditions such as Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Psoriatic Arthritis (PsA) is well established. A recent population-based cohort study quantified the risk of MACE among patients with RA, PsA, and psoriasis compared to the general population after adjusting for traditional cardiovascular risk factors. The risk of MACE was elevated by 40-50% in patients with RA but only 20% in patients with PsA. Our group has explored potential mechanisms to explain the attenuated risk of MACE in PsA compared to RA. Previous clinical studies have suggested that increased serum levels of IL-10 are associated with a more favorable prognosis in patients with acute coronary syndromes.  Murine models have shown IL-10 to have atheroprotective effects. IL-10 has also been shown to favorably effect reverse cholesterol transport in THP-1 macrophages via increases in the expression of ABCA1, ABCG1, and Liver X receptor α. We sought to determine if IL-10 present in PsA plasma modulated the expression of the major cellular cholesterol transport proteins ABCA1 and CD36, and prevented foam cell formation.

Methods:  The study was performed under a Winthrop University Hospital IRB-approved protocol. Level of IL-10 was evaluated by ELISA (Milliplex). THP-1 differentiated macrophages (10⁶/ml, phorbol dibutyrate, 100nM, 48h), were incubated (37⁰C, 5% C0₂, 18h) ± 1, 10, 50 and 100 pg/ml of recombinant human IL-10 ± 100 ng/ml of anti-IL10 (R&D) for neutralization.  Macrophages were exposed to 10% plasma from 8 PsA±100 ng/ml of anti-IL10 (R&D). Expression of major cholesterol transport proteins: ATP binding cassette transporter (ABC) A1 and CD36 were quantified by real-time PCR, foam cells were identified by oil-red-O staining.

Results: Purified IL-10 had a bimodal effect on expression of the cholesterol efflux gene ABCA1. ABCA1 was increased by IL-10 1.3±0.04 fold at 10 pg/ml and reaching 2.4±0.2 fold at 50 pg/ml (n=3, P<0.05) but had no effect at 100 pg/ml. Neutralization of IL-10 by anti-IL10 antibody decreased the expression of ABCA1 to the baseline level of untreated cells. CD36 expression was not affected.

In THP-1 macrophages exposed to 10 % PsA plasma (~24 pg/ml) inhibition of IL-10 binding significantly decreased expression of ABCA1 71±9.0% (n=8, P<0.001) with expression in macrophages exposed to PsA plasma set at 100%. In addition, neutralization of IL-10 increased expression of CD36 to 133.4±6.9% (n=8, P<0.001). Results were confirmed by Western blot. Consequently, neutralization of IL-10 increased foam cell formation by 20%.

Conclusion: Compared to pro-atherogenic changes induced by RA plasma, PsA plasma displays a modest pro-atherogenic pattern consistent with the clinically observed attenuated risk of MACE in PsA compared to RA. IL-10 in PsA plasma demonstrates an artheroprotective effect on cellular cholesterol transport. This study suggests a role for IL-10 in the attenuation of MACE observed in PsA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-10-may-mitigate-cardiovascular-risk-in-psoriatic-arthritis-via-an-anti-atherosclerotic-effect-on-cellular-cholesterol-transport/