Pharmacological targets of metabolism in disease: Opportunities from macrophages

Pharmacol Ther. 2020 Jun:210:107521. doi: 10.1016/j.pharmthera.2020.107521. Epub 2020 Mar 6.

Abstract

From advances in the knowledge of the immune system, it is emerging that the specialized functions displayed by macrophages during the course of an immune response are supported by specific and dynamically-connected metabolic programs. The study of immunometabolism is demonstrating that metabolic adaptations play a critical role in modulating inflammation and, conversely, inflammation deeply influences the acquisition of specific metabolic settings.This strict connection has been proven to be crucial for the execution of defined immune functional programs and it is now under investigation with respect to several human disorders, such as diabetes, sepsis, cancer, and autoimmunity. The abnormal remodelling of the metabolic pathways in macrophages is now emerging as both marker of disease and potential target of therapeutic intervention. By focusing on key pathological conditions, namely obesity and diabetes, rheumatoid arthritis, atherosclerosis and cancer, we will review the metabolic targets suitable for therapeutic intervention in macrophages. In addition, we will discuss the major obstacles and challenges related to the development of therapeutic strategies for a pharmacological targeting of macrophage's metabolism.

Keywords: Autoimmunity; Cancer; Immunometabolism; Macrophage; Metabolic immunotherapy; Mitochondria; Therapy.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Atherosclerosis / drug therapy
  • Atherosclerosis / immunology
  • Atherosclerosis / metabolism
  • Cell Lineage
  • Energy Metabolism* / drug effects
  • Humans
  • Immunologic Factors / therapeutic use
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Metabolic Diseases / drug therapy
  • Metabolic Diseases / immunology
  • Metabolic Diseases / metabolism
  • Metabolome* / drug effects
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Phenotype
  • Tumor-Associated Macrophages / drug effects
  • Tumor-Associated Macrophages / immunology
  • Tumor-Associated Macrophages / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Immunologic Factors