Turning up the heat: immune brinksmanship in the acute-phase response.

The acutephase response (APR) is a systemic response to severe trauma, infection, and cancer, although many of the numerous cytokine-mediated components of the APR are incompletely understood. Some of these components, such as fever, reduced availability of iron and zinc, and nutritional restriction due to anorexia, appear to be stressors capable of causing harm to both the pathogen and the host. We review how the host benefits from differences in susceptibility to stress between pathogens and the host. Pathogens, infected host cells, and neoplastic cells are generally more stressed or vulnerable to additional stress than the host because: (a) targeted local inflammation works in synergy with APR stressors; (b) proliferation/growth increases vulnerability to stress; (c) altered pathogen physiology results in pathogen stress or vulnerability; and (d) protective heat shock responses are partially abrogated in pathogens since their responses are utilized by the host to enhance immune responses. Therefore, the host utilizes a coordinated system of endogenous stressors to provide additional levels of defense against pathogens. This model of immune brinksmanship can explain the evolutionary basis for the mutually stressful components of the APR.