title: Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome. The Sepsis Intervention Group.
abstract: OBJECTIVE
  To assess the value of measuring circulating concentrations of mediators (endotoxin, tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], and interleukin-6[IL-6]) and their endogenous antagonists (antiendotoxin core antibody [EndoCAb], interleukin-1 receptor antagonist [IL-1ra], and soluble TNF receptors [sTNF-R]) in predicting mortality and organ failure in sepsis syndrome.
  
  
  METHODS
  Cohort study with a follow-up period of 30 days.
  
  
  METHODS
  Intensive therapy units of five tertiary referral centers in Scotland.
  
  
  METHODS
  A total of 146 intensive therapy unit patients with sepsis syndrome underwent repeated sampling during a 10-day period following admission to an intensive therapy unit.
  
  
  METHODS
  Circulating concentrations of mediators and antagonists were compared in survivors and nonsurvivors.
  
  
  RESULTS
  Median Acute Physiology and Chronic Health Evaluation II score was 23 (range, 8 to 40). Mortality at 30 days was 49%. On entry to the study, circulating endotoxin was detected in 66% of patients, TNF-alpha in 14%, and IL-1 beta in 29%. Levels did not predict mortality or organ failure. Patients with IL-6 concentrations in excess of 3000 pg/mL had an increased mortality rate (64% vs 40%, P = .02). The incidence of IgG EndoCAb depletion on entry to the study was 26% in nonsurvivors and 10% in survivors (P = .02). Initial concentrations of both type I and type II sTNF-R were significantly higher in nonsurvivors (P < .01). Initial circulating IL-1ra concentrations were not of value in predicting mortality. Cytokine antagonists were present in concentrations 30- to 100,000-fold greater than their corresponding cytokine.
  
  
  CONCLUSIONS
  The observed high circulating levels of the cytokine antagonists IL-1ra and sTNF-R and the relatively small proportion of patients developing EndoCAb depletion may contribute to the limitations of therapies that aim to augment natural defenses against endotoxin or the proinflammatory cytokines.
authors.affiliation: University Department of Surgery, Royal Infirmary, Edinburgh, Scotland.
authors.forename: A S
authors.initials: AS
authors.lastname: Goldie
authors.forename: K C
authors.initials: KC
authors.lastname: Fearon
authors.forename: J A
authors.initials: JA
authors.lastname: Ross
authors.forename: G R
authors.initials: GR
authors.lastname: Barclay
authors.forename: R E
authors.initials: RE
authors.lastname: Jackson
authors.forename: I S
authors.initials: IS
authors.lastname: Grant
authors.forename: G
authors.initials: G
authors.lastname: Ramsay
authors.forename: A S
authors.initials: AS
authors.lastname: Blyth
authors.forename: J C
authors.initials: JC
authors.lastname: Howie
mesh_terms: D018806:APACHE; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000992:Antitoxins / Q000097:blood*; D015331:Cohort Studies; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000097:blood*; D004731:Endotoxins / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007136:Immunoglobulins / Q000097:blood*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D017741:Survivors; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000992:Antitoxins; D016207:Cytokines; D004731:Endotoxins; D007136:Immunoglobulins; D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha