Inflammation-induced metabolic derangements or adaptation: An immunometabolic perspective

Inflammatory mediators have a well-established role in mediating metabolic disturbances. Chronic low-grade inflammation is implicated in the pathogenesis of obesity and the development of metabolic syndrome. This phenomenon is even more pronounced in severe inflammatory states such as in critically ill patients where hyperglycaemia invariably manifests. Similarly, though inflammatory mediators have a well-established role in promoting bone resorption, the adaptive function of this process remains unknown. Here we review emerging evidence from the field of immunometabolism suggesting that these two processes serve a common goal, namely, to sustain the rapid proliferation of immune cells during an infection. Activated immune cells exhibit an increased demand for glucose which not only provides energy, but also glycolytic intermediates which are fluxed into biosynthetic processes. Similarly, phosphate liberated from bone is consumed during the phosphorylation of glycolytic intermediates, which plays a critical role in the synthesis of nucleotides and phospholipids. Taken together, these considerations suggest that metabolic alterations induced by inflammatory mediators do not manifest as an inability to maintain homeostatic levels of metabolites but represent an adaptive shift in the homeostatic set point during an infection.