title: High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. The Swiss-Dutch J5 Immunoglobulin Study Group.
abstract: OBJECTIVE
  We measured the serum concentrations of interleukin-6 (IL-6) in 70 patients with established septic shock caused predominantly by gram-negative bacteria. The aims of the study were to determine whether and for how long IL-6 was detectable in the circulation of these patients, to assess whether IL-6 levels were associated with patients' outcomes, and, finally, to examine the interplay between IL-6, tumor necrosis factor (TNF), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma).
  
  
  RESULTS
  IL-6 was detected in 64% of the patients at study entry but in only 18% on Day 1 and 2% on Day 10. Serum levels of IL-6 were higher (median: 3.5 ng/mL, range: less than 0.1 to 305 ng/mL) in patients dying of fulminant septic shock than in those surviving (median: 0.5 ng/mL, range: less than 0.1 to 135 ng/mL; p = 0.003) or in those with a transient reversal of shock but who ultimately died of a relapse of shock (median: less than 0.1 ng/mL, range: less than 0.1 to 12.5 ng/mL; p = 0.005). However, no cutoff values of IL-6 confidently predicted the outcome of an individual patient. The serum concentrations of IL-6 measured at study entry correlated with the duration of survival (r = -0.51, p = 0.004) and with the levels of TNF-alpha (r = 0.53; p less than 0.0001) but not with the levels of either IL-1 beta (r = 0.01, p = 0.90) or IFN-gamma (r = 0.06, p = 0.60).
  
  
  CONCLUSIONS
  These results indicate that circulating levels of IL-6 are detectable in a majority of patients with gram-negative septic shock. Concentrations of IL-6 peaked near the onset of shock and rapidly decreased to undetectable levels within approximately 24 hours in most patients. Levels of IL-6 measured at study entry correlated with levels of TNF and with patients' outcomes. Yet, IL-6 does not appear to be a clinically useful laboratory test for predicting the outcome of an individual patient.
authors.affiliation: Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Calandra
authors.forename: J
authors.initials: J
authors.lastname: Gerain
authors.forename: D
authors.initials: D
authors.lastname: Heumann
authors.forename: J D
authors.initials: JD
authors.lastname: Baumgartner
authors.forename: M P
authors.initials: MP
authors.lastname: Glauser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012044:Regression Analysis; D012772:Shock, Septic / Q000097:blood*; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma