Figure 1.
Cotrimoxazole has multiple anti-inflammatory effects in people living with HIV. Graphical summary of the anti-inflammatory effects of cotrimoxazole identified using samples from the ARROW trial and complimentary in vitro models.29 Effects of cotrimoxazole include (a) reduced circulating inflammatory mediators (CRP and IL-6), (b) suppression of viridans group streptococci (VGS), a type of bacteria that lives in the gut and promotes intestinal inflammation, which can be measured by stool levels of myeloperoxidase (MPO; a neutrophil-derived reactive oxygen species involved in antimicrobial immune responses). Stool MPO is an indicator of neutrophil accumulation and activity in the gut mucosa, (c) inhibition of pro-inflammatory mediator production (TNFα and IL-6) by immune cells activated by being experimentally exposed to bacteria, and 4) suppression of neutrophil chemoattractant protein production (IL-8) by gut epithelial cells. IL-8 is one of the signals that attracts neutrophils to the gut mucosa and perpetuates intestinal inflammation. IL-8 production is also stimulated by mevalonate pathway metabolites.