Fever, hyperthermia, and the lung: it's all about context and timing

Although body temperature is tightly regulated in humans, elevated temperatures are frequently encountered during febrile illnesses and exertional and environmental hyperthermia. Such temperature increases exert profound effects on cell signaling and gene expression patterns, which have important consequences for innate immune function and cell injury, apoptosis, and recovery. The lung offers a framework for understanding how these effects can either benefit or harm the host. We present data demonstrating that exposure to febrile-range hyperthermia (∼39.5 °C) exerts multiple biologic effects that converge on enhanced neutrophil recruitment to the lung, and describe the consequences of these effects for pathogen clearance and collateral tissue injury. We also discuss the influence of temperature on apoptosis in lung epithelium. Collectively, the data presented identify body temperature as a modifiable factor that exerts profound influence on the outcome of infection and injury.