PURPOSE AND PATIENTS: 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.