Active resolution of inflammation is a previously unrecognized process essential for tissue homeostasis. Monocytes and macrophages are central components of the immune system. During infection and inflammation they play a pivotal role not only in the generation of inflammatory mediators and regulation of innate and adaptive immune responses but they also actively contribute to resolution of inflammation by producing anti-inflammatory cytokines and removal of pro-inflammatory pathogens, cellular debris and apoptotic cells present at later stages of inflammation. Diversity and plasticity are hallmarks of monocytes and macrophages. Glucocorticoids (GC) are still the most widely used drugs in the treatment of a wide range of chronic and autoimmune diseases acting on cells of the immune system, including monocytes and macrophages. It was generally believed, that anti-inflammatory actions of GC on monocytes and macrophages are mainly due to the suppression of their function. Our studies have shown that treatment of naive monocytes with GC does not cause the global suppression of monocytic effector function, but rather induces differentiation of cells with anti-inflammatory and regulatory phenotype (regulatory monocytes, Mreg). However, the exact mechanism of GC action on monocytes and macrophages during inflammation is still not completely elucidated. Analysis of the effects of GC on lipopolysaccharide (LPS)-triggered proinflammatory monocytes demonstrated that, also in this case, GC do not simply suppress LPS-mediated activation of monocytes but rather induce their reprogramming toward a specific anti-inflammatory phenotype which actively promotes resolution of inflammation. Unravelling specific GC-actions on monocytes may thus define novel pathways allowing anti-inflammatory therapy without enhanced risk for severe infections.
Disclosure of Interest None declared