title: Critically ill anergic patients demonstrate polymorphonuclear neutrophil activation in the intravascular compartment with decreased cell delivery to inflammatory focci.
abstract: Skin test anergy, the failure to produce a delayed type hypersensitivity (DTH) response, is associated with an increase in infection-related complications and death usually due to multiple organ failure (MOF). Refractory intravascular activation of polymorphonuclear neutrophils (PMNs) has been implicated in the development of MOF. We studied 20 critically ill surgical patients with life threatening infections to determine if PMN intravascular activation was present and how this affected essential PMN functions such as exudation. The 11 anergic patients had a more intense inflammatory response to their infection. Plasma lactoferrin was 6.1 +/- 0.3 microgram/ml in anergic patients compared to 3.9 +/- 1.5 in reactive P less than 0.05, accompanied by reduced total primary (3.3 +/- 1.9 vs 4.7 +/- 2.1 micrograms/10(6) PMN P less than 0.01) and secondary (2.8 +/- 0.4 vs 5.0 +/- 0.9 microgram/10(6) PMN P less than 0.01) granule content, respectively. In vitro superoxide production following 100 ng/ml PMA stimulation was 0.44 +/- 0.1 in anergics vs 0.36 +/- 0.1 nmol/microgram PMN protein in reactivities, P less than 0.05. PMN chemotaxis was 8.2 +/- 0.6 PMNs/HPF in anergics compared to 10.2 +/- 1.6 PMNs/HPF in reactives P less than 0.05, accompanied by decreased PMN delivery to skin blister windows (3.2 +/- 1.4 vs 4.5 +/- 1.9 x 10(7) PMN/ml, respectively, P less than 0.05). We conclude that critically ill anergic surgical patients have increased intravascular PMN activation, which may contribute to oxygen-derived tissue damage in the vascular space, as well as a deficient delivery of effector cells in areas of bacterial invasion. This may lead to inability to clear the inflammatory signals which set up the vicious circle of MOF leading to death.
authors.affiliation: Department of Surgery, McGill University, Montreal, Quebec, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Tellado
authors.forename: N V
authors.initials: NV
authors.lastname: Christou
mesh_terms: D002448:Cell Adhesion; D015550:Cell Degranulation; D002634:Chemotaxis, Leukocyte; D005122:Exudates and Transudates; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007781:Lactoferrin / Q000097:blood; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D016897:Respiratory Burst; D012882:Skin Tests; D013481:Superoxides / Q000378:metabolism; D013514:Surgical Procedures, Operative
chemical_list: D016177:Macrophage-1 Antigen; D013481:Superoxides; D005966:Glucuronidase; D007781:Lactoferrin