Resolution of inflammation in immune and nonimmune cells by interleukin-19

Abstract

The inflammatory response is a complex, tightly regulated process activated by tissue wounding, foreign body invasion, and sterile inflammation. Over the decades, great progress has been made to advance our understanding of this process. One often overlooked aspect of inflammation is its sequel: resolution. We know that dysregulated resolution often results in numerous chronic degenerative diseases such as arthritis, cancer, and asthma. However, identification of components and mechanisms of resolving pathways lags behind those of proinflammatory processes, yet represents overlooked therapeutic opportunities. One approach is identification of endogenous, negative compensatory mechanisms, which are activated in response to inflammation for the purpose of resolution of that inflammatory stimuli. This review will focus on literature that describes expression and function of interleukin-19, a proposed anti-inflammatory cytokine, in numerous inflammatory diseases. The literature concerning IL-19 is complex, context-dependent, and often contradictory. The expression and function of IL-19 in the inflammatory response are in no way settled. We will attempt to clarify the role that this interesting and understudied cytokine plays in resolution of inflammation and discuss its mechanisms of action in different cell types. We will present a hypothesis that endogenous IL-19 expression in response to inflammatory stimuli is a cellular compensatory mechanism to dampen inflammation. We further present studies suggesting that while endogenously expressed IL-19 may be a response to inflammation, pharmacological levels may be necessary to effectively resolve the inflammatory cascade.