Therapeutic targeting of the inflammome

Inflammatory responses can vary depending on a myriad of factors including: (1) the initiating stimulus or trigger, (2) the cell types involved in the response, and (3) the specific effector cytokine–chemokine milieus produced. The compilation of these and other factors in a given mechanistic context is sometimes referred to as the “inflammome”. Humans and other higher-order mammals have evolved (over time) several discrete inflammomes to counter the effects of pathogens. However, when these inflammomes are induced inappropriately, they drive the development of chronic inflammatory diseases. The vast majority of biological anti-inflammatory treatments currently being developed are focused on the post hoc inhibition of downstream effectors by anti-cytokine monoclonal antibodies and receptor antagonists. This prevailing “end-point treatment” has even directed a new disease classification paradigm, namely a cytokine-based disease classification, as opposed to a traditional diagnosis based on a particular tissue or organ system dysfunction. Although this approach has a number of advantages, it omits the processes that led to the generation of the inflammatory effectors in the first place. In this review, we will expand the cytokine-based disease taxonomy into an inflammome-based taxonomy that includes interventions that subvert a priori cytokine development and can complement post hoc inhibition.

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