Inhibiting the NLRP3 Inflammasome With Methylene Blue as Treatment Adjunct in Myelodysplasia

Abstract

Myelodysplasia refers to a group of clonal hematopoietic neoplasms characterized by genetic heterogeneity, different clinical behaviors and prognoses. Some of this group of bone marrow failure conditions have known external causes, some are of unknown origin. Within marrow, intracellular, and extracellular elements of the innate immune system are activated and contribute to creation of multiple cytogenetic abnormalities and are central to the mode of hematopoietic cell failure. Basiorka et al. showed that NLRP3 inflammasome activity is essential to the innate immune system's destruction of marrow hematopoietic cells commonly in myelodysplasia. In April 2018 Hao et al. reported that methylene blue inhibits rat NLRP3 inflammasome function. Methylene blue has been in continuous use in humans for over a century. It is associated with an eminently benign side effect profile in human use. If as in rodents, methylene blue also inhibits NLRP3 inflammasome function in human myelodysplasia a trial of adjunctive methylene blue treatment in transfusion dependent, low risk myelodysplasia where marrow inflammation and apoptosis predominates, would be worth trying.HIGHLIGHTS - Cytogenetic abnormalities and innate immune activation are seen in myelodysplasia- The NLRP3 inflammasome is a core element generating marrow failure of myelodysplasia- In April 2018 methylene blue was reported to potently inhibit NLRP3 inflammasome function- Methylene blue has benign side effects and has been in human use for a century- Study of methylene blue treatment of myelodysplasia would be a low-risk intervention

In Vitro Evaluation of the Antiviral Activity of Methylene Blue Alone or in Combination against SARS-CoV-2

“…Methylene blue could reduce hypoxia, one of the main complications in COVID-19 patients, by decreasing methemoglobin. Moreover, methylene blue decreases inflammation and oxidative stress [ 48 , 49 ]. Pro-inflammatory cytokines and nitric oxide were considerably increased in the cytokine storm due to COVID-19 [ 50 ].…”

Multimodal quantitative imaging of brain cancer in cultured cells

“…Our group is investigating the potential of fluorescence polarization (FP) imaging [14] for cancer detection. Specifically, we focus on FP exhibited by exogenous methylene blue (MB), a phenothiazinium dye approved by the United States Food and Drug Administration for several clinical indications [15,16]. Previously, we demonstrated that MB enhanced contrast of brain neoplasms [17,18].…”

Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications

“…MB improves mitochondrial function by inducing peroxisome proliferator-activated receptor γ coactivator 1 PGC1α, a central mediator of mitochondrial biogenesis [56], and downregulates the expression of NACHT, Leucine-rich repeat (LRR), and Pyrin (PYD) dominions that contain protein 3 (NLRP3) an inflammasome produced by bone marrow derivatives from macrophages induced by ATP. In addition, MB might regulate inflammation, influencing the signaling way of pro-inflammatory nuclear factor-κB (NF-κB) and inhibiting caspase-1 activation to reduce apoptosis [57].…”