Luke O’Neill: How mitochondria control cytokines

How mitochondria control cytokines

Mitochondrial disturbance is a feature of inflammatory cells, and we have been analysing mitochondrial metabolites, notably itaconate and fumarate in inflammatory macrophages. Itaconate derivatives are anti-inflammatory and have potential for the treatment of immune and inflammatory diseases. We have found that the cytokine GDF-15 is a key signal being driven by itaconate and fumarate, as well as general disturbance of mitochondria. It has anti-inflammatory effects, can limit food intake and thereby control obesity, and may act to take the pressure off damaged mitochondria in inflammation. Overall evidence is growing that a break in mitochondrial endosymbiosis might be a reason for the increasing incidence of autoimmune and inflammatory diseases. These insights are providing a new view of metabolism in immunity and inflammation and might indicate new therapeutic approaches.