Background Antimalarial drugs (AMs) namely hydroxychloroquine (HCQ) have been shown to reduce disease activity and prevent flares of patients with systemic lupus erythematosus (SLE).1,2 Despite some evidence highlighting the immunomodulatory properties,2 the mechanism through which HCQ adjusts immune system and reverses disease activity is not completely known. Some scientists have proposed that HCQ has a regulatory effect on the pro-inflammatory cytokines.2
Objectives To assess the effect of HCQ therapy on disease activity and serum levels of immunologic biomarkers in patients with SLE.
Methods In this prospective cohort study, newly diagnosed patients were included. Patients requiring immunosuppressive drugs except prednisolone at doses lower than 10 mg/day were excluded. The patients were evaluated in baseline visit (before commencement of HCQ therapy) as well as in 2 follow-up visits (1 and 2 months after beginning the HCQ therapy) according to the following parameters: serum levels of IL-6, IL-8 and TNF-α (pg/mL) using ELISA kits (Orgenium Labs, Vantaa, Finland), serum levels of CH50 (U/mL) using ELISA kits (DRG International Inc., Springfield, USA) and disease activity using the Systemic Lupus Erythaematosus Disease Activity Index (SLEDAI-2K). Serum levels of the cytokines and CH50 of 14 age-matched healthy controls (HCs) were also assessed to serve as a comparison with baseline results in SLE patients. Variables are presented with median and interquartile range (IQR). Friedman's test was used to analyze differences in the mean ranks of each parameter. The differences of the immunologic biomarkers between HCs and patients were analyzed by Mann-Whitney U test.
Results Fourteen female patients with median (IQR) age of 29 (24.8-36.0) years were studied. Serum levels of IL-6 (16.7 (6.8-49.5) vs. 1.6 (1.5-2.1), p<0.001) and TNF-α (20.8 (6.9-130.5) vs. 4.9 (5.4-5.8), p<0.001) were significantly higher in SLE patients compared to HCs. Conversely, CH50 level was significantly lower in SLE patients compared to HCs (74.0 (56.5-88.8) vs. 98.4 (73.2-124.3), p=0.042). IL-8 levels were not significantly different between Patients and HCs. HCQ therapy resulted in significant decrease in SLEDAI-2K (17.0 (7.3-20.0) to 3.0 (0.0-6.0), p<0.001), IL-6 (16.7 (6.8-49.5) to 6.5 (4.1-448.5), p=0.003) and TNF-α (20.8 (6.9-130.5) to 7.6 (4.2-70.8), p=0.001) from the baseline visit to 3rd visit (Figure 1). Moreover, CH50 levels significantly improved from 74.0 (56.5-88.8) to 96.5 (71.5-121.0) (p=0.014). No significant change in serum levels of IL-8 was observed during the 2-month follow-up.
Conclusions HCQ is effective on clinical improvement of SLE patients, reduction of pro-inflammatory cytokines and normalizing the complement activity. These provide evidence that HCQ can induce immunomodulation through adjustment of pro-inflammatory cytokines and complement activity.
Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, et al. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010;69:20-8.
Willis R, Seif AM, McGwin G Jr, et al. Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort. Lupus. 2012;21:830-5.
Disclosure of Interest None declared