title: Divergent invariant natural killer T-cell response to sepsis of abdominal vs. non-abdominal origin in human beings.
abstract: BACKGROUND
  The etiology of sepsis is broad. The peritoneal cavity displays compartmentalization with respect to inflammatory responses, so peripheral blood responses to sepsis of abdominal vs. non-abdominal origin are expected to be divergent. Lymphocytes and invariant natural killer T (iNKT) cells play important roles in survival from sepsis, as they dampen the neutrophil and macrophage responses. We assessed whether circulating iNKT cells display distinct phenotypic profiles depending on the presence of abdominal vs. non-abdominal infection with sepsis.
  
  
  METHODS
  Patients with sepsis, defined as infection confirmed microbiologically with a systemic inflammatory response syndrome (SIRS), were enrolled prospectively. They were categorized as having either exclusively sepsis of abdominal or exclusively non-abdominal origin. The white blood cell (WBC) count was recorded. Whole-blood staining with monoclonal antibodies to CD3, V-alpha-24 (to identify iNKT cells), and CD69 (marker of early activation) was applied.
  
  
  RESULTS
  Of the 53 enrolled patients, 18 had abdominal infection. Pneumonia was the most common non-abdominal type. There was no difference in gender, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, WBC count, or CD3(+) T cells (7.1%±1.6% vs. 6.5%±0.9%; p=0.75) in the two groups. Patients with abdominal infection had a higher proportion of iNKT cells (2.7%±1.1% vs. 0.89%±0.14%; p=0.032). Correcting for WBC count, this translated into a higher absolute number of iNKT cells (3.4±1.8×10(7)/L vs. 0.74±0.15×10(7)/L; p=0.03). Patients with sepsis of abdominal origin had a lower percentage of CD69(+) iNKT cells (9.1%±3.1% vs. 27.2%±5.8%; p=0.028). In patients in shock vs. those who were not, patients with non-abdominal infection exhibited a greater number of iNKT cells (1.47±0.3 v. 0.62±0.1×10(7)/L; p=0.022) and percentage of activated iNKT cells (53±14.5% vs. 17.9±4.8%; p=0.04). Patients with non-abdominal infection who died had a lower absolute number of activated iNKT cells (0.8±1.2×10(7)/L vs. 0.34±0.1×10(7)/L; p=0.023); however, no such shock or death correlation was noted in patients with sepsis of abdominal origin.
  
  
  CONCLUSIONS
  Divergent sepsis etiologies display distinct blood iNKT cell population changes. In non-abdominal infection, this difference was associated with septic shock and death. Elucidating the importance and basis for these changes relative to the response to sources of infection will help clarify appropriate diagnosis and management of the patient with sepsis.
authors.affiliation: Division of Surgical Research, Department of Surgery, The Alpert School of Medicine at Brown University/Rhode Island Hospital , Providence, Rhode Island.
authors.forename: John S
authors.initials: JS
authors.lastname: Young
authors.forename: Sean F
authors.initials: SF
authors.lastname: Monaghan
authors.forename: Chun S
authors.initials: CS
authors.lastname: Chung
authors.forename: William G
authors.initials: WG
authors.lastname: Cioffi
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
authors.forename: Daithi S
authors.initials: DS
authors.lastname: Heffernan
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D059413:Intraabdominal Infections / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology*; D011014:Pneumonia / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D011446:Prospective Studies; D018805:Sepsis / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D012772:Shock, Septic / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis