Effect of add-on hydroxychloroquine therapy on serum pro-inflammatory cytokine levels in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease in which autoantibodies, immune complexes, and inflammation can damage multiple organ systems
.
The pathogenesis of systemic lupus erythematosus involves a complex interplay of immune, genetic, and environmental factors, and several studies have identified associations between several pro-inflammatory cytokine levels and SLE disease activity and specific clinical manifestations
.
Levels of interferon (IFN) and IFN-induced chemokines have been reported to correlate with disease activity, as measured
by disease activity indices such as erythrocyte sedimentation rate and anti-dsDNA antibody titers.
Other pro-inflammatory cytokines shown to be associated with SLE disease activity include tumor necrosis factor-α (TNF-α), interleukin(IL)-6, IL-8, IL-10, and vascular endothelial growth factor (VEGF).

HCQ therapy has been reported to have a modulating effect on interferon in patients with SLE
.
However, few reports have been reported on the effects of HCQ on inflammatory cytokines, and little is known about the effects on biomarkers when HCQ is additionally used in SLE patients who maintain LDA with conventional care
.
In this study, the effect
of add-on HCQ on pro-inflammatory cytokine levels in SLELDA patients receiving immunosuppressants was studied.

Serum levels
of tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, IL-8, vascular endothelial growth factor (VEGF)-A, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and interleukin-1 receptor antagonists (IL-1ra) were measured before and 3 months after oral HCQ treatment 。 In the 51 patients participating in the study, HCQ treatment resulted in a significant reduction in serum TNF-α, IL-6, IL-8, VEGF-A, IL-1ra, and IL-2 levels (p < 0.
0001; p = 0.
0006; p = 0.
0460，p = 0.
0177; p <0.
0001; p = 0.
0282) and MIP-1α levels decreased (but not significant) (p = 0.
0746).

No significant changes were observed in serum MCP-1 levels before and after HCQ administration (p=0.
1402).

The results of this study suggest that add-on HCQ therapy can modulate the expression
of pro-inflammatory cytokines even in patients with systemic lupus erythematosus with low disease activity.

serum cytokine levels before and after hydroxychloroquine treatment:

Overall, the investigators found that add-on HCQ therapy reduced serum levels
of several pro-inflammatory cytokines in SLELDA patients.
Its findings suggest that add-on HCQ therapy may reduce pro-inflammatory cytokine expression
in SLE patients.
Long-term prospective studies are needed to clarify whether pro-inflammatory cytokine regulation caused by add-on HCQ therapy is associated with
improved SLE outcomes or relapse prevention.

References: Wakiya R, Ueeda K, Nakashima S, Shimada H, Kameda T, Mansour MMF, Kato M, Miyagi T, Sugihara K, Mizusaki M, Mino R, Kadowaki N, Dobashi H.
Effect of add-on hydroxychloroquine therapy on serum proinflammatory cytokine levels in patients with systemic lupus erythematosus.
Sci Rep.
2022 Jun 17; 12(1):10175.
doi: 10.
1038/s41598-022-14571-6.
PMID: 35715525; PMCID: PMC9205904.