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Journal of Immunology Research
Volume 2015, Article ID 697193, 11 pages
Review Article

Reconciling the IPC and Two-Hit Models: Dissecting the Underlying Cellular and Molecular Mechanisms of Two Seemingly Opposing Frameworks

1Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biology, University of Brasilia, 70910-900 Brasilia, DF, Brazil
2Laboratory of Surgical Physiopathology (LIM-62), Faculty of Medicine, University of Sao Paulo, 01246-904 Sao Paulo, SP, Brazil

Received 3 September 2015; Revised 10 November 2015; Accepted 18 November 2015

Academic Editor: Carlos Rosales

Copyright © 2015 Carlos F. M. Morris et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.