Hydroxychloroquine inhibits proinflammatory signalling pathways by targeting endosomal NADPH oxidase

Müller‐Calleja, Nadine; Manukyan, Davit; Canisius, Antje; Strand, Dennis; Lackner, Karl J.

doi:10.1136/annrheumdis-2016-210012

Cited by 88 publications

(77 citation statements)

References 53 publications

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“…46 And more recently in an in vitro experiment, HCQ has been shown to target endosomal nicotinamide adenine dinucleotide phosphate oxidase the enzymatic activity of which is involved in many inflammatory and prothrombotic signaling pathways. 47 Although there is not a general consensus about the exact mechanism of action, the effects of HCQ on lipid profiles in lupus patients is apparent based on our meta-analysis. Of note, there were conflicting reports of HCQ's effect on the serum LDL level in patients with mild SLE.…”

Section: Discussionmentioning

confidence: 89%

Favorable effects of hydroxychloroquine on serum low density lipid in patients with systemic lupus erythematosus: A systematic review and meta‐analysis

et al. 2017

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Aims: Hydroxychloroquine (HCQ) has shown to have significant immunomodulatory effects in the treatment of systemic lupus erythematosus (SLE). Current studies show favorable effects of HCQ on traditional cardiac risk factors in patients with SLE. This review examined the effects of HCQ on serum low-density lipoprotein (LDL) level in patients with SLE.Methods: A systematic search of seven major literature search databases from their inception until 3 April, 2017 identified nine studies. Random-effects pooled mean difference with corresponding 95% confidence intervals (CI) were estimated. Heterogeneity was measured by I 2 . Publication bias was assessed by visual inspection of funnel plots. Sensitivity analysis examined whether HCQ effect on serum total cholesterol level was similar to the main analysis. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the overall quality of evidence.Results: Pooled study participants were 559 patients from eight observation studies (two before-after studies; six case-control studies) examining the effects of HCQ on serum LDL. Pooled study participants' characteristics were as follows: mean age 45.719, female 95.262%, and prednisone use 58.366%. HCQ reduced mean LDL levels by 24.397 mg/dL (95% CI 8.921-39.872; P = 0.002). The number of studies identifying statin use was too few to perform meta-regression analysis of statin use. Heterogeneity was extensive (I 2 = 94.739%). Symmetrical funnel plot visualized no evidence of publication bias.Conclusion: HCQ was associated with serum LDL level reduction by mean 24.397 mg/dL in patients with SLE. Future prospective studies are need to fully characterize the treatment effect.

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Section: Discussionmentioning

confidence: 89%

Favorable effects of hydroxychloroquine on serum low density lipid in patients with systemic lupus erythematosus: A systematic review and meta‐analysis

et al. 2017

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“…Moreover, NADPH oxidase (NOX2), a multimeric complex of gp91phox, p67phox, p47phox, p22phox, and small G protein Rac, catalyzes the production of superoxide to play an important role in oxidative stress and inflammation (Bylund et al 2010). The gp91phox is the catalytic subunit of NOX2 and interestingly, HCQ attenuates the translocation of gp91phox to the membrane (Muller-Calleja et al 2017), leading to the inhibition of oxidative stress and proinflammatory signaling pathways. Therefore, CQ/HCQ treatment may be beneficial for COVID-19 patients via its antioxidant and anti-inflammatory properties ( Fig.…”

Section: Inhibition Of Proinflammatory Molecules By Hcqmentioning

confidence: 99%

Smooth or Risky Revisit of an Old Malaria Drug for COVID-19?

Pahan

2020

J Neuroimmune Pharmacol

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Hydroxychloroquine (HCQ) is an old medication for malaria. In addition to handling this parasitic disease, HCQ is also used to treat a number of autoimmune disorders including rheumatoid arthritis and systemic lupus erythematosus when other medications are not effective. Recently a new viral infection (COVID-19) is rocking the entire world so much that it has already taken more than 200,000 lives throughout the world within the last two months and the World Health Organization was forced to declare it as a pandemic on March 11, 2020. Interestingly, some reports indicate that this wonder drug may be also beneficial for COVID-19 and accordingly, many clinical trials have begun. Here, we discuss different modes of action (anti-inflammatory, antioxidant, inhibition of endosomal acidification, suppression of angiotensin-converting enzyme 2 or ACE2 glycosylation, etc.) of HCQ that might be responsible for its possible anti-COVID-19 effect. On the other hand, this review also makes an honest attempt to delineate mechanisms (increase in vasoconstriction, inhibition of autophagy, depletion of T cells, etc.) indicating how it may aggravate certain conditions and why caution should be taken before granting widespread repurposing of HCQ for COVID-19.

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“…60 Inhibits TNFα, IL-1β and aPL-mediated induction of endosomal NOX, in human monocytes and MonoMac1 cells by inhibiting the translocation of gp91phox, catalytic subunit of NOX2. 100 Adenosine pathway…”

Section: Methotrexatementioning

confidence: 99%

Mechanism based pharmacodynamic interactions of glucocorticoids and DMARDs- A review

Chandrashekara¹

2018

IJIR

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Combination of conventional disease-modifying antirheumatic drugs (cDMARDs), which assist in achieving effective disease control and functional outcomes in rheumatoid arthritis (RA), is widely accepted as an effective treatment regimen. Steroid is often used in combination with DMARDs and there are several uncertainties associated with the regimen, including the therapeutic benefits of the combination. Further understanding the pharmacodynamics and mechanism of actions of steroids and possible drug interactions may assist in improving the treatment outcomes. While the treatment has shown to be effective with better outcome, the use of steroids in the combination regime has been a topic of contradiction.The pharmacodynamic actions of corticosteroids and cDMARDs is variable and overlapping in some domains. In a highly dynamic and constantly adopting immune system, the expression of receptors and signal pathways depends on various factors including the status of cytokine and antigen load. The pattern of introduction of the drugs is one of the major challenges that hampers the effective use of synergism and other interactions associated with the combination. Understanding the drug mechanism and interaction pathways and their variability is essential for customizing the treatment strategies. This review article addresses the current trends of combined treatment in the management of RA. It is also aimed at providing consolidated information on the pharmacodynamic interactions of glucocorticoids and DMARDs in RA.

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Hydroxychloroquine inhibits proinflammatory signalling pathways by targeting endosomal NADPH oxidase

Cited by 88 publications

References 53 publications

Favorable effects of hydroxychloroquine on serum low density lipid in patients with systemic lupus erythematosus: A systematic review and meta‐analysis

Favorable effects of hydroxychloroquine on serum low density lipid in patients with systemic lupus erythematosus: A systematic review and meta‐analysis

Smooth or Risky Revisit of an Old Malaria Drug for COVID-19?

Mechanism based pharmacodynamic interactions of glucocorticoids and DMARDs- A review

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