Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Effect of Hydroxychloroquine and Statin Therapy on Pro-Inflammatory Cytokines and Disease Activity in a Lupus Cohort.
Willis1, Rohan, Jajoria1, Praveen, Harper1, Brock E., Gonzalez1, Emilio B., Petri2, M., Akhter2, Ehtisham, Fang2, Hong
Multiple cytokines play a role in the immune dysregulation seen in SLE and the local inflammatory responses that ultimately lead to tissue injury. IL6, TNFa, sCD40L, IFNa and IFN inducible cytokines such as MCP1 and IP10 are correlated with disease activity as measured by the SLEDAI, SLAM-R, ESR and anti-dsDNA antibody titres. Elevated VEGF and IL1b levels have been demonstrated in patients (pts) with antiphospholipid syndrome.
Both hydroxychloroquine (HCQ) and statins have proven clinical efficacy in treating SLE patients. There is however limited data highlighting the effect HCQ and statins have on biomarkers of disease activity in SLE. As such we sought to determine the proinflammatory biomarkers elevated in these pts and the effect that HCQ or statin therapy has on their levels and on disease activity.
Pts were selected from a longitudinal cohort and were included if placed on HCQ or statin therapy during follow-up and had stored serum or plasma samples taken before and after commencement of therapy at least 6 months apart. Serum samples from age and sex matched controls with no evidence of inflammatory disease were used for comparison. Concurrent use of prednisone greater than 10mg/day or change in use or dose of other immunosuppressive agents precluded inclusion. Samples from 30 controls and 61 paired samples from SLE pts were analyzed. IFNa2, IL1b, IL6, IL8, IP10, MCP1, TNFa, VEGF and sCD40L levels were determined by the MILLIPLEXMAP human cytokine/chemokine panel assay (Millipore, Billerica, MA). This assay utilizes flow cytometry, microspheres, lasers, digital signal processing and traditional chemistry in a multiplex format. Disease activity was assessed using SLEDAI scores.
VEGF, IP10, sCD40L, IFNa2 and TNFa were significantly elevated (p= <0.0001 0.0478) in SLE pts compared to controls while MCP1 and IL8 were significantly lower. No difference was seen with IL6 and IL1b. Both statin and HCQ therapy resulted in decreased SLEDAI scores although these were not statistically significant (p= 0.07 and 0.30 respectively). Elevated VEGF, IP10, sCD40L, IFNa2 or TNFa at baseline were reduced by 16.3 41.0% as a result of statin therapy and by 15.4 44.9% as a result of HCQ therapy. When considering all subjects in the SLE cohort, the changes in biomarkers were not statistically significant.
This study shows that proinflammatory cytokines in SLE patients are significantly elevated when compared to controls. Although the treatment with HCQ or with statins produced a decrease in the levels of cytokines in the subjects where those markers were elevated at baseline, no differences were seen in SLEDAI scores after the treatment with HCQ or statins, possibly due to the limited sample size (due to a strict inclusion/exclusion criteria) and/or the relatively low disease activity scores of the subjects in this lupus cohort.
|Cytokines||Ctrls/Median||SLE/Median||p-value||# elevated baseline samples HCQ therapy(%)||% reduction in elevated samples after HCQ/mean||# elevated baseline samples statin therapy(%)||% reduction in elevated samples after statin/mean|
|IL8||27.4||3.44||<0.0001||3/33 (9.1)||93.9 ± 5.2||4/28 (14.2)||72.5 ± 48.4|
|IL6||0||0||0.2971||10/33 (30.3)||39.6 ± 50.1||5/28 (17.9)||58.82 ± 53.73|
|VEGF||88.3||146.27||0.0178||20/33 (60.6)||18.6 ± 29.7||15/28 (53.6)||16.3 ± 21.6|
|MCP1||884.28||230.08||<0.0001||2/33 (6.0)||39.2 ± 55.5||0||0|
|IP10||96.22||335.51||<0.0001||30/33 (90.9)||20.7 ± 27.1||25/28 (89.3)||14.7 ± 24.0|
|sCD40L||16.39||719.95||<0.0001||31/33 (93.9)||44.9 ± 41.6||28/28 (100)||35.1 ± 43.1|
|INFa2||0||9.22||0.0478||14/33 (42.4)||15.4 ± 32.5||11/28 (39.3)||39.6±48.5|
|IL1b||0||0||0.5442||8/33 (24.2)||60.5 ± 44.7||8/28 (28.6)||65.6 ± 46.9|
|TNFa||0||6.93||<0.0001||20/33 (60.6)||32.9 ± 34.2||18/28 (64.3)||41.0 ± 39.6|
To cite this abstract, please use the following information:
Willis, Rohan, Jajoria, Praveen, Harper, Brock E., Gonzalez, Emilio B., Petri, M., Akhter, Ehtisham, et al; Effect of Hydroxychloroquine and Statin Therapy on Pro-Inflammatory Cytokines and Disease Activity in a Lupus Cohort. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :613