Host responses in mediating sepsis and adult respiratory distress syndrome.
Despite significant advances in intensive care unit technology and mechanical ventilatory support, mortality due to adult respiratory distress syndrome (ARDS) or multiorgan failure (MOF) has not changed significantly within the past two decades. The key to improving survival requires understanding and modifying (or eliminating) factors that may initiate (or modulate) these syndromes. Infection, and the host responses to infection, are major etiological factors responsible for the induction and perpetuation of the injury to the lung and microvasculature in ARDS and MOF, and contribute to late mortality. While the pathogenesis of ARDS and MOF-complicating sepsis remains to be elucidated, bacterially derived (eg, endotoxin or lipopolysaccharides [LPS]) and host-derived humoral and cellular mediators are of importance in both disease states. In fact, the host response to infection (or injurious stimuli) may be a more critical determinant of the outcome of sepsis and ARDS than the original inciting stimulus. The pleiotropic effects of LPS are largely indirect, and are orchestrated via its ability to trigger the release of an array of host-derived mediators of inflammation. Several potential mechanisms of injury in ARDS, sepsis, and MOF have been suggested and include a variety of inflammatory cells (neutrophils, mononuclear phagocytes, platelets), activated complement and coagulation components, vasoactive mediators (kinins, arachidonic acid metabolites, lipids, peptides), reactive oxygen radicals, and diverse cytokines. Interactions between these humoral and cellular mediators appear to set in motion an amplified cascade of events culminating in cellular and tissue injury. In this article, several of these putative inflammatory mediators are discussed in detail, and the importance of cytokine networking and the possible role of nonimmune cells in the orchestration of the inflammatory response associated with ARDS and MOF are explained. Finally, future therapeutic strategies aimed at blocking or suppressing the release or effects of endogenous mediators may be the key to improving the outcome of these disorders.
Strieter
R M
RM
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor.
Lynch
J P
JP
Basha
M A
MA
Standiford
T J
TJ
Kasahara
K
K
Kunkel
S L
SL
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology; D003165:Complement System Proteins / Q000276:immunology; D003428:Cross Infection / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D010450:Endopeptidases / Q000276:immunology; D006801:Humans; D007362:Intensive Care Units; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000502:physiology; D009102:Multiple Organ Failure / Q000276:immunology*; D010972:Platelet Activating Factor / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D012128:Respiratory Distress Syndrome / Q000276:immunology*
D001095:Arachidonic Acids; D016207:Cytokines; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D003165:Complement System Proteins; D010450:Endopeptidases