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SOD mimetic inhibits immune response in cerebral malaria

cigana

cigana

Senior Member
Messages
1,095
Location
UK
It is interesting how this suggests that immune activation can be inhibited by an enzyme that prevents oxidative stress:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087140

We undertook testing Tempol—a superoxide dismutase (SOD) mimetic and pleiotropic intracellular antioxidant—in cells relevant to malaria pathogenesis in the context of coagulation and inflammation. Tempol was also tested in a murine model of CM induced by Plasmodium berghei Anka infection. Tempol was found to prevent transcription and functional expression of procoagulant tissue factor in endothelial cells (ECs) stimulated by lipopolysaccharide (LPS). This effect was accompanied by inhibition of IL-6, IL-8, and monocyte chemoattractant protein (MCP-1) production. Tempol also attenuated platelet aggregation and human promyelocytic leukemia HL60 cells oxidative burst. In dendritic cells, Tempol inhibited LPS-induced production of TNF-α, IL-6, and IL-12p70, downregulated expression of co-stimulatory molecules, and prevented antigen-dependent lymphocyte proliferation. Notably, Tempol (20 mg/kg) partially increased the survival of mice with CM. Mechanistically, treated mice had lowered plasma levels of MCP-1, suggesting that Tempol downmodulates EC function and vascular inflammation. Tempol also diminished blood brain barrier permeability associated with CM when started at day 4 post infection but not at day 1, suggesting that ROS production is tightly regulated.
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A user on this forum @Bluebrid has found this mimetic to be very helpful.
 
B

Bluebrid

Messages
14
Tempol is often used in research to test whether or not a condition is related to free radical stress. Interesting that Tempol attenuated the hyper-coagulation and inflammatory response to cerebral malaria. It is most likely due to the improved cell signaling.

One of the infections I contracted prior to taking Tempol was severe babesiosis. Babesia is considered a “cousin” of malaria. Most people are able to clear babesia on their own. However with my genes, free radical stress and the toxins I had encountered, babesia was shutting down my immune system. The clotting issues were so bad, they thought I was having mini strokes -- and then I was hospitalized with a DVT and PEs. 2/3 of my lungs were full of clots by the time I got to the hospital.

In retrospect, the integrative MD said that the SOD SNP is most likely the reason I was not able to handle the babesiosis without intervention. As I had not yet found Tempol -- and it took over 6 months of high dose malaria meds to clear the infection. The meds, infections and clotting issues definitely took a toll on my body.
 
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