Critical illness-related corticosteroid insufficiency and community-acquired pneumonia: back to the future!

I n the past decade, emphasis in the study of the pathogenesis of infectious diseases has shifted from determining the function of the cellular players in the inflammatory response to the mediators that orchestrate activation and regulation of this response [1]. According to current thinking, pulmonary sepsis begins when pathogens invade the sterile lower respiratory tract, leading to activation of the innate immune response to produce local and systemic inflammation [2]. Whereas restricted inflammation is beneficial, excessive or persistent inflammation incites tissue destruction and disease [3]; it is the lack of regulation (dysregulated systemic inflammation) of this vital response that is central to the pathogenesis of sepsis-associated morbidity and mortality [2, 4]. Among patients with community-acquired pneumonia (CAP), nonsurvivors, unlike survivors, exhibit persistent elevation in plasma inflammatory cytokine levels over time [5–7].