Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex pathogenesis. Published data have revealed that serum levels of proinflammatory cytokines are increased in SLE patients. The aim of our study was to evaluate whether monotherapy with chloroquine phosphate affects IL-1beta, IL-6, IL-18 and TNF-alpha serum levels in SLE patients. The study group consisted of 25 SLE patients with mild or moderate disease activity and 25 age- and sex-matched healthy control subjects. In SLE patients the cytokine levels were measured just before and three months after starting chloroquine treatment at a dose of 125 mg twice daily. Although the majority of SLE patients had a low systemic lupus activity measure (SLAM) index, the levels of IL-6, IL-18 and TNF-alpha were significantly higher than in the control group. After three-months of chloroquine therapy the mean level of IL-6, IL-18 and TNF-alpha decreased significantly. Minimal erythema doses (MEDs) were significantly increased in SLE patients after three months of chloroquine therapy. The results indicate that chloroquine treatment lowers some proinflammatory cytokines and may provide a photoprotective effect.

Antimalarial drugs inhibit IFNα-enhanced TNFα and STAT4 expression in monocytes: Implication for systemic lupus erythematosus

“…Thus, patients were classified in IFNa-low and IFNa-high using the percentile 80 obtained in healthy controls (n = 45) as cut off (P80 = 29.25 pg/ml). In agreement with previous results [20,21], antimalarial treated SLE patients showed strikingly lower levels of TNFa (81.14%) compared to those without such treatment (86.88 (107.03) vs 16.39 (60.94) pg/ml)). STAT4 gene expression tends to decrease in patients under antimalarial treatment (64.90 (52.46) vs 57.24 (69.49), n.s.…”

“…Despite some uncertainty regarding the exact mechanisms underlying their antiinflammatory effects, in vitro studies showed that chloroquine interferes with the expression of TNFa and other proinflammatory cytokines [17,19], probably by affecting the cellular lysosomal acidification [18]. Also, studies in SLE patients showed that antimalarial treatment reduces serum levels of TNFa [20,21], thus suggesting that cytokine inhibition may be involved in a beneficial outcome. Accordingly, our results confirmed that chloroquine treatment inhibits the in vitro production of TNFa by healthy LPS-stimulated monocytes, but, in addition, we demonstrated this inhibitory effect even when TNFa induction is enhanced by IFNa, an expected situation in most SLE patients.…”

“…It is well known that antimalarial therapy inhibits the production of TNFa and other proinflammatory cytokines [20,21], thus we wanted to determine the influence of these drugs on the production of TNFa induced by IFNa. As is shown in Fig.…”

“…It has been described that antimalarials prevent lupus flares and increase long-term survival of SLE patients [15,16], probably due to their ability to downregulate the production of TNFa and other proinflammatory cytokines, demonstrated in vitro by stimulated human monocytes [17][18][19], and in SLE patients [20,21]. Although the mechanisms for antimalarials are not completely known, it has been described they may block the TLR interaction with nucleic acid ligands by altering lysosomal acidification and disrupting endosomal maturation [22], constituting an interesting therapy for the IFNa blockade, which could prevent the activation of proinflammatory pathways.…”

IL-18 105 A>C polymorphism contributes to renal manifestations in patients with SLE

“…IL-18 can contribute to the pathogenesis of various disorders including liver cirrhosis, type I diabetes, rheumatoid arthritis, Crohn's disease and SLE [10][11][12][13][14][15][16]. It has been reported that IL-18 concentrations are significantly higher in blood plasma of SLE patients than in control subjects [14][15][16].…”