title: Immunopathologic responses to non-lethal sepsis.
abstract: Although sepsis causes significant morbidity and mortality, its basic pathology is still not well understood. We investigated the inflammatory and physiologic alterations of non-lethal sepsis using cecal ligation and puncture (CLP), a model that induces peritonitis due to mixed intestinal flora, reproducing the complex immunology of sepsis. Groups of mice were subjected to CLP (25G needle) or sham surgery, had minimitters implanted to continuously monitor temperature and activity, and were sacrificed daily for 6 days. There was significant hypothermia (6-13 hrs post-surgery), and decreases in activity (to day 4) and weight (to day 3) but no mortality in the CLP group. Blood analyses of the CLP-treated mice showed reduced hemoglobin, platelets, lymphocytes, monocytes, and neutrophils, compared to sham animals. Both groups had nearly equivalent neutrophil influx into the peritoneum. Plasma and peritoneal G-CSF, IL-6, as well as the murine chemokines KC and MIP2-alpha were significantly higher in the CLP-treated mice at day 1. Plasma and peritoneal TNF were low (<70 pg/mL). While there was elevated IL-1beta in the peritoneum of the CLP-treated mice, this cytokine was not detected in the plasma in either treatment group. Cytokines were not detected in the pulmonary airspace of the CLP-treated mice and PMNs were not recruited to this site. Our data shows altered immunopathology in non-lethal sepsis with significant blood and cytokine alterations. Since there was 100% survival, the inflammatory response was appropriate and probably even protective.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Ebong
authors.forename: D R
authors.initials: DR
authors.lastname: Call
authors.forename: G
authors.initials: G
authors.lastname: Bolgos
authors.forename: D E
authors.initials: DE
authors.lastname: Newcomb
authors.forename: J I
authors.initials: JI
authors.lastname: Granger
authors.forename: M
authors.initials: M
authors.lastname: O'Reilly
authors.forename: D G
authors.initials: DG
authors.lastname: Remick
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001833:Body Temperature Regulation; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D002940:Circadian Rhythm; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000378:metabolism*; D009043:Motor Activity; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism; D018805:Sepsis / Q000473:pathology / Q000503:physiopathology*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015431:Weight Loss
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D006454:Hemoglobins; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; C074302:keratinocyte-derived chemokines