title: Multiple organ dysfunction syndrome: end organ and systemic inflammatory response in a mouse model of nonseptic origin.
abstract: The authors measured the peripheral blood pro-inflammatory cytokine responses (tumor necrosis factor-alpha [TNF-alpha] and interleukin-6 [IL-6]) and related end organ responses ti intraperitoneal zymosan-saline suspension over 5 days in CD-1 mice. Other indicators of local and systemic inflammation included wet:dry weight ratios of lung, liver, kidneys, spleen, and bowel; peripheral blood hematocrit, white blood cell count, and platelet count; lung myeloperoxidase activity; lung protein leak; and bacterial translocation to liver, spleen, and mesenteric lymph nodes. The initial event in responses to zymosan A injection was a sharp rise in the peripheral blood TNF-alpha level, which crested within 1 h of injection. This response was followed by a peripheral blood leukocytosis also within 1 h, and a peak lung myeloperoxidase activity within 1-2 h of injection. The maximum lung permeability index occurred 8 h after injection (zymosan, .398 +/- .019 [n = 10]; saline vehicle, .266 +/- .007 [n = 10], p < .001) followed by the maximum lung wet:dry weight ratio, which occurred 18 h after injection. The peak wet:dry weight ratios for the other organs occurred between 12 and 24 h after injection as well. Peripheral blood IL-6 maxima followed TNF-a maxima after lags of several hours. The release of pre-formed TNF-a is likely the most proximal event following injection of zymosan, and may set in motion the processes that result in end-organ injury and secondary multiple organ dysfunction, particularly activation of leukocytes. The precise roles of TNF-alpha and IL-6 in the pathogenesis of end-organ injury, however, are not addressed.
authors.affiliation: Departments of Anesthesiology, University of Michigan Medical School, Ann Arbor 48109-0211, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Shayevitz
authors.forename: C
authors.initials: C
authors.lastname: Miller
authors.forename: K J
authors.initials: KJ
authors.lastname: Johnson
authors.forename: J L
authors.initials: JL
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D001772:Blood Cell Count; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D006400:Hematocrit; D007249:Inflammation / Q000097:blood* / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009102:Multiple Organ Failure / Q000097:blood* / Q000473:pathology; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D013577:Syndrome
chemical_list: D016207:Cytokines; D009195:Peroxidase