Sepsis: a pro- and anti-inflammatory disequilibrium syndrome.
Severe sepsis and probably most prolonged critical illnesses reflect a paradox of combined increased activation and depression of the immune apparatus. The increased activation of the inflammatory response is evidenced from the increased levels of circulating proinflammatory cytokines in the blood, increased endothelial activation with increased expression of inducible nitric oxide synthase, and increased de novo CD11b expression on circulating immune effector cells, such as PMNs, monocytes and lymphocytes. However, coexisting with this proinflammatory process is a profound anti-inflammatory state characterized by increased circulating levels of anti-inflammatory species that both directly block the binding of proinflammatory stimuli to their cell surface receptors (IL-1ra, soluble TNF receptors) and also induce an anti-inflammatory state on their own (IL-10, TFG-beta). This humoral anti-inflammatory state is mirrored at the cellular levels by decreased monocyte ability to process antigen, characterized by a reduced HLA-DR expression and impaired PMN upregulation in response to clearly proinflammatory stimuli. Accordingly, severe sepsis reflects a combined pro- and anti-inflammatory state. Both the pro- and anti-inflammatory arms have protective and destructive aspects, making their modulation by treatment less predictable than if their actions were purely beneficial or detrimental.
Pinsky
M R
MR
Anesthesiology, Critical Care Medicine and Medicine, Division of Critical Care Medicine, University of Pittsburgh, Pa., USA. pinskymr@anes.upmc.edu
D006684:HLA-DR Antigens / Q000032:analysis; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D016177:Macrophage-1 Antigen / Q000097:blood; D008928:Mitochondria / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology*
D006684:HLA-DR Antigens; D006360:Heat-Shock Proteins; D016177:Macrophage-1 Antigen; D016328:NF-kappa B