title: Reconciling the IPC and Two-Hit Models: Dissecting the Underlying Cellular and Molecular Mechanisms of Two Seemingly Opposing Frameworks.
abstract: Inflammatory cascades and mechanisms are ubiquitous during host responses to various types of insult. Biological models and interventional strategies have been devised as an effort to better understand and modulate inflammation-driven injuries. Amongst those the two-hit model stands as a plausible and intuitive framework that explains some of the most frequent clinical outcomes seen in injuries like trauma and sepsis. This model states that a first hit serves as a priming event upon which sequential insults can build on, culminating on maladaptive inflammatory responses. On a different front, ischemic preconditioning (IPC) has risen to light as a readily applicable tool for modulating the inflammatory response to ischemia and reperfusion. The idea is that mild ischemic insults, either remote or local, can cause organs and tissues to be more resilient to further ischemic insults. This seemingly contradictory role that the two models attribute to a first inflammatory hit, as priming in the former and protective in the latter, has set these two theories on opposing corners of the literature. The present review tries to reconcile both models by showing that, rather than debunking each other, each framework offers unique insights in understanding and modulating inflammation-related injuries.
authors.affiliation: Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biology, University of Brasilia, 70910-900 Brasilia, DF, Brazil.
authors.forename: Carlos F M
authors.initials: CF
authors.lastname: Morris
authors.affiliation: Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biology, University of Brasilia, 70910-900 Brasilia, DF, Brazil.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Tahir
authors.affiliation: Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biology, University of Brasilia, 70910-900 Brasilia, DF, Brazil; Laboratory of Surgical Physiopathology (LIM-62), Faculty of Medicine, University of Sao Paulo, 01246-904 Sao Paulo, SP, Brazil.
authors.forename: Samina
authors.initials: S
authors.lastname: Arshid
authors.affiliation: Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biology, University of Brasilia, 70910-900 Brasilia, DF, Brazil.
authors.forename: Mariana S
authors.initials: MS
authors.lastname: Castro
authors.affiliation: Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biology, University of Brasilia, 70910-900 Brasilia, DF, Brazil.
authors.forename: Wagner
authors.initials: W
authors.lastname: Fontes
mesh_terms: D000818:Animals; D032921:Consensus; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology* / Q000517:prevention & control; D019194:Ischemic Preconditioning; D008954:Models, Biological; D015427:Reperfusion Injury / Q000276:immunology* / Q000517:prevention & control