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

Wakiya, Risa; Ueeda, Kiyo; Nakashima, Shusaku; Shimada, Hiromi; Kameda, Tomohiro; Mansour, M. H.; Kato, M.; Miyagi, T.; Sugihara, Koichi; Mizusaki, Mao; Mino, Rina; Kadowaki, Norimitsu; Dobashi, Hiroaki

doi:10.1038/s41598-022-14571-6

Cited by 6 publications

(3 citation statements)

References 46 publications

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“…There is conflicting data regarding the effect of HCQ on serum levels of IL-8. While Wakiya et al [ 42 ] showed a negative effect of HCQ, others did not observe any changes [ 43 , 44 ]. Therefore, it remains unresolved to what extent the levels of these cytokine relate to the severity of PE and its phenotypes [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Hydroxychloroquine on Primary Feto-Placental Endothelial Cells from Healthy and Early-Onset Preeclamptic Placentas

Schröder‐Heurich

Mercnik

et al. 2023

IJMS

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Hydroxychloroquine (HCQ), an anti-malarial drug, is suggested as a promising candidate for the treatment of pregnancy-related disorders associated with endothelial activation, among which there is preeclampsia (PE). Arterial feto-placental endothelial cells (fpECAs) were isolated from control (CTR) and early-onset preeclamptic (EO-PE) placentas. The aim of this study was to test potential protective effects of HCQ in an in vitro model of endothelial activation as well as in cells isolated from EO-PE placentas. To mimic PE conditions, CTR fpECAs were exposed to a pro-inflammatory environment consisting of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1β (furtherly referred as MIX) with or without varying concentrations of HCQ (1 µg/mL and 10 µg/mL). Their effect on wound healing and endothelial barrier integrity was analyzed. Variations in the expression of IL-8 and leukocyte adhesion molecules (LAM) on both mRNA and protein levels were determined between CTR and PE fpECAs in the presence or absence of HCQ. MIX decreased wound healing and stability of the endothelial barrier, but HCQ did not affect it. Significant differences between CTR and EO-PE fpECAs were observed in IL-8 mRNA, protein secretion, and vascular cell adhesion protein 1 (VCAM-1) mRNA expression levels. After challenging CTR fpECAs with MIX, upregulation of both mRNA and protein levels was observed in all molecules. Combined treatment of HCQ and MIX slightly lowered VCAM-1 total protein amount. In CTR fpECAs, treatment with low concentrations of HCQ alone (1 µg/mL) reduced basal levels of IL-8 and VCAM-1 mRNA and secretion of IL-8, while in EO-PE fpECAs, a higher (10µg/mL) HCQ concentration slightly reduced the gene expression of IL-8. Conclusion: These results provide additional support for the safety of HCQ, as it did not adversely affect endothelial functionality in control fpECAs at the tested concentration. Furthermore, the observed limited effects on IL-8 secretion in EO-PE fpECAs warrant further investigation, highlighting the need for clinical trials to assess the potential therapeutic effects of HCQ in preeclampsia. Conducting clinical trials would offer a more comprehensive understanding of HCQ’s efficacy and safety, allowing us to explore its potential benefits and limitations in a real-world clinical setting.

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Section: Discussionmentioning

confidence: 99%

The Impact of Hydroxychloroquine on Primary Feto-Placental Endothelial Cells from Healthy and Early-Onset Preeclamptic Placentas

Schröder‐Heurich

Mercnik

et al. 2023

IJMS

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“…On the other hand, hydroxychloroquine (HQC) has been used to treat inflammatory diseases such as SLE, other autoimmune and neoplastic disorders, and metabolic and infectious diseases. When HQC is used in patients with SLE, some signs and symptoms, such as fatigue, skin rashes, joint pain, mouth ulcers, and arthralgia, improve and inhibit the production of inflammatory cytokines [74,75]. In addition, a decrease in aortic stiffness, systemic vascular resistance, and increased elasticity of the large arteries has been noticed; therefore, HQC therapy in SLE exerts a protective effect on coronary artery disease [76,77].…”

Section: Cardiovascular Clinical Assessments In Slementioning

confidence: 99%

Biomarkers in Systemic Lupus Erythematosus along with Metabolic Syndrome

Corona-Meraz,

Vázquez-Del Mercado,

Sandoval-García

et al. 2024

JCM

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Metabolic syndrome (MetS) is a group of physiological abnormalities characterized by obesity, insulin resistance (IR), and hypertriglyceridemia, which carry the risk of developing cardiovascular disease (CVD) and type 2 diabetes (T2D). Immune and metabolic alterations have been observed in MetS and are associated with autoimmune development. Systemic lupus erythematosus (SLE) is an autoimmune disease caused by a complex interaction of environmental, hormonal, and genetic factors and hyperactivation of immune cells. Patients with SLE have a high prevalence of MetS, in which elevated CVD is observed. Among the efforts of multidisciplinary healthcare teams to make an early diagnosis, a wide variety of factors have been considered and associated with the generation of biomarkers. This review aimed to elucidate some primary biomarkers and propose a set of assessments to improve the projection of the diagnosis and evolution of patients. These biomarkers include metabolic profiles, cytokines, cardiovascular tests, and microRNAs (miRs), which have been observed to be dysregulated in these patients and associated with outcomes.

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“…Several cytokines are implicated in the pathogenesis of AAV, especially IL-6, IL-8, IL-10, IL-17 and TNF-α (tumour necrosis factor alpha) [98] . HCQ has been shown to inhibit the production of IL-6, IL-17 and TNF-α (possibly by inhibiting TLR pathways), in addition to other cytokines like IL-1, IL-2, IL-22, IFN-α (interferon alpha), and IFN-gamma [99,100] .…”

mentioning

confidence: 99%

Hydroxychloroquine as a potential therapy for ANCA-associated vasculitis

Jain,

Sangle,

Kim

et al. 2024

Vessel Plus

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Antimalarial agents have been used to treat various autoimmune rheumatic diseases for over a century. Hydroxychloroquine is a safe, effective and inexpensive antimalarial drug with additional antithrombotic, cardioprotective, antimicrobial, and anti-neoplastic benefits. It has been used extensively in various diseases, especially systemic lupus erythematosus and rheumatoid arthritis; however, it has not been used in anti-neutrophil cytoplasmic antibody associated vasculitides (AAVs). There exists a significant unmet need for safe and inexpensive treatments for non-severe AAV or those with low-grade “grumbling” disease activity who do not warrant significant escalation of therapy but who remain at risk of disease flares and damage accumulation. Hydroxychloroquine may be an option to help fill this void. Although the mechanisms of action of Hydroxychloroquine are not fully understood, it interacts with various inflammatory mediators involved in the pathogenesis of AAV. Based on these benefits, along with the unmet need in AAV, we present evidence to support the use of Hydroxychloroquine as a potential therapy for AAV.

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

Cited by 6 publications

References 46 publications

The Impact of Hydroxychloroquine on Primary Feto-Placental Endothelial Cells from Healthy and Early-Onset Preeclamptic Placentas

The Impact of Hydroxychloroquine on Primary Feto-Placental Endothelial Cells from Healthy and Early-Onset Preeclamptic Placentas

Biomarkers in Systemic Lupus Erythematosus along with Metabolic Syndrome

Hydroxychloroquine as a potential therapy for ANCA-associated vasculitis

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