Targeting immunometabolism as an anti-inflammatory strategy

Cell Res. 2020 Apr;30(4):300-314. doi: 10.1038/s41422-020-0291-z. Epub 2020 Mar 4.

Abstract

The growing field of immunometabolism has taught us how metabolic cellular reactions and processes not only provide a means to generate ATP and biosynthetic precursors, but are also a way of controlling immunity and inflammation. Metabolic reprogramming of immune cells is essential for both inflammatory as well as anti-inflammatory responses. Four anti-inflammatory therapies, DMF, Metformin, Methotrexate and Rapamycin all work by affecting metabolism and/or regulating or mimicking endogenous metabolites with anti-inflammatory effects. Evidence is emerging for the targeting of specific metabolic events as a strategy to limit inflammation in different contexts. Here we discuss these recent developments and speculate on the prospect of targeting immunometabolism in the effort to develop novel anti-inflammatory therapeutics. As accumulating evidence for roles of an intricate and elaborate network of metabolic processes, including lipid, amino acid and nucleotide metabolism provides key focal points for developing new therapies, we here turn our attention to glycolysis and the TCA cycle to provide examples of how metabolic intermediates and enzymes can provide potential novel therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use*
  • Autoimmune Diseases* / drug therapy
  • Autoimmune Diseases* / metabolism
  • Dimethyl Fumarate / pharmacology
  • Dimethyl Fumarate / therapeutic use
  • Glycolysis / drug effects
  • Humans
  • Immunomodulation*
  • Immunosuppressive Agents / therapeutic use*
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Metformin / pharmacology
  • Metformin / therapeutic use
  • Methotrexate / pharmacology
  • Methotrexate / therapeutic use
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Immunosuppressive Agents
  • Metformin
  • Dimethyl Fumarate
  • Sirolimus
  • Methotrexate