Resolving chronic inflammation
Under physiological conditions, self-resolving inflammation is beneficial for the host as it is an immune-mediated process of clearing the antigenic stimulus. Appropriate resolution of inflammatory responses activates repair mechanisms and ensures that tissues return to homeostasis. However, the chronic evolution of inflammation is a key determinant of immunopathology and clinical manifestations of many diseases in humans, including autoimmune diseases, obesity, neurodegeneration and cancer. As a result, understanding how and why inflammation fails to resolve is of outmost medical importance. Towards this goal, the EU-funded TIMER (Targeting novel mechanisms of resolution in inflammation) project set out to identify the molecular players of inflammation resolution. Using natural resources and chemical strategies, researchers managed to define novel anti-inflammatory drugs, which control inflammation. They identified different mechanisms that regulate resolution of inflammation through microRNAs or metabolic molecules such as succinate. Other molecules such as TIR8 also worked as promoters of resolution by inhibiting the cytokine TLR system. Furthermore, researchers identified specific atypical chemokine receptors, decoy receptors and plant extracts that served as pro-resolving agents. They generated significant insight into their mechanism of action and their anti-inflammatory impact in vivo. Clinical trials on the TLR7 agonist TMX-101 indicated the safety and efficacy of the compound in resolving inflammation in humans. The project team scheduled future additional trials for anti-chemokine antibodies or antagonists of chemokine receptors. Overall, TIMER findings offer novel insight into the mechanism of inflammation resolution. Through identification of the determinants in the process, researchers proposed to treat inflammation through its resolution and not by blocking it.
Keywords
Inflammation, autoimmune diseases, anti-inflammatory, succinate, chemokine receptors
