Interleukin-6 (IL-6) is likely to be an important mediator of the inflammatory response. We measured levels of this cytokine in plasma samples from 37 patients with sepsis or septic shock obtained at the time of admission to the intensive care unit and related these levels to hemodynamic and biochemical parameters as well as to clinical outcome. In 32 of the 37 patients, increased levels of IL-6 were found, occasionally up to 7,500 times the normal level. The highest IL-6 levels were encountered in patients who suffered from septic shock (P value of the difference between patients with and without shock less than .0001). In addition, IL-6 significantly correlated with plasma lactate (P less than .0001), heart rate (P = .05) and, inversely, with mean arterial pressure (P = .01) and platelet counts (P = .0002). Significant correlations of IL-6 with the anaphylatoxins C3a (P = .0001) and C4a (P = .0002) and with the main inhibitor of the classical pathway of complement, C1-inhibitor (inverse correlation, P = .05), were also observed. IL-6 on admission appeared to be of prognostic significance: levels were higher in septic patients who subsequently died than in those who survived (P = .0003), in particular when only patients with septic shock were considered (P less than .0001). All nine septic patients with levels of less than 40 U/mL on admission survived, whereas 89% of the nine patients with levels exceeding 7,500 U/mL died. These data provide evidence for a role of IL-6 in the pathophysiology of septic shock. Further studies are needed to reveal whether IL-6 in sepsis is directly involved in mediating lethal complications or whether it is to be considered as an “alarm hormone” that reflects endothelial cell injury probably mediated by the anaphylatoxines.

Interleukin-6 (IL-6) is likely to be an important mediator of the inflammatory response. We measured levels of this cytokine in plasma samples from 37 patients with sepsis or septic shock obtained at the time of admission to the intensive care unit and related these levels to hemodynamic and biochemical parameters as well as to clinical outcome. In 32 of the 37 patients, increased levels of IL-6 were found, occasionally up to 7,500 times the normal level. The highest IL-6 levels were encountered in patients who suffered from septic shock (P value of the difference between patients with and without shock less than .0001). In addition, IL-6 significantly correlated with plasma lactate (P less than .0001), heart rate (P = .05) and, inversely, with mean arterial pressure (P = .01) and platelet counts (P = .0002). Significant correlations of IL-6 with the anaphylatoxins C3a (P = .0001) and C4a (P = .0002) and with the main inhibitor of the classical pathway of complement, C1-inhibitor (inverse correlation, P = .05), were also observed. IL-6 on admission appeared to be of prognostic significance: levels were higher in septic patients who subsequently died than in those who survived (P = .0003), in particular when only patients with septic shock were considered (P less than .0001). All nine septic patients with levels of less than 40 U/mL on admission survived, whereas 89% of the nine patients with levels exceeding 7,500 U/mL died. These data provide evidence for a role of IL-6 in the pathophysiology of septic shock. Further studies are needed to reveal whether IL-6 in sepsis is directly involved in mediating lethal complications or whether it is to be considered as an “alarm hormone” that reflects endothelial cell injury probably mediated by the anaphylatoxines.

Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock. To monitor contact activation in patients with sepsis, we developed highly sensitive radioimmunoassays (RIAs) for factor XIIa-Cl(- )-inhibitor (Cl(-)-Inh) and kallikrein-Cl(-)-Inh complexes using a monoclonal antibody (MoAb Kok 12) that binds to a neodeterminant exposed on both complexed and cleaved Cl(-)-Inh. Plasma samples were serially collected from 48 patients admitted to the intensive care unit because of severe sepsis. Forty percent of patients on at least one occasion had increased levels of plasma factor XIIa-Cl(-)-Inh (greater than 5 x 10(-4) U/mL) and kallikrein-Cl(-)-Inh (greater than 25 x 10(- 4) U/mL), that correlated at a molar ratio of approximately 1:3. Levels of factor XII antigen in plasma and both the highest as well as the levels on admission of plasma factor XIIa-Cl(-)-Inh in 23 patients with septic shock were lower than in 25 normotensive patients (P = .015: factor XII on admission; P = .04: highest factor XIIa-Cl(-)-Inh; P = .01: factor XIIa-Cl(-)-Inh on admission). No significant differences in plasma kallikrein-Cl(-)-Inh or prekallikrein antigen were found between these patients' groups. Elevated Cl(-)-Inh complex levels were measured less frequently in serial samples from patients with septic shock than in those from patients without shock (P less than .0001). Based on these results, we conclude that plasma Cl(-)-Inh complex levels during sepsis may not properly reflect the extent of contact activation.

Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock. To monitor contact activation in patients with sepsis, we developed highly sensitive radioimmunoassays (RIAs) for factor XIIa-Cl(- )-inhibitor (Cl(-)-Inh) and kallikrein-Cl(-)-Inh complexes using a monoclonal antibody (MoAb Kok 12) that binds to a neodeterminant exposed on both complexed and cleaved Cl(-)-Inh. Plasma samples were serially collected from 48 patients admitted to the intensive care unit because of severe sepsis. Forty percent of patients on at least one occasion had increased levels of plasma factor XIIa-Cl(-)-Inh (greater than 5 x 10(-4) U/mL) and kallikrein-Cl(-)-Inh (greater than 25 x 10(- 4) U/mL), that correlated at a molar ratio of approximately 1:3. Levels of factor XII antigen in plasma and both the highest as well as the levels on admission of plasma factor XIIa-Cl(-)-Inh in 23 patients with septic shock were lower than in 25 normotensive patients (P = .015: factor XII on admission; P = .04: highest factor XIIa-Cl(-)-Inh; P = .01: factor XIIa-Cl(-)-Inh on admission). No significant differences in plasma kallikrein-Cl(-)-Inh or prekallikrein antigen were found between these patients' groups. Elevated Cl(-)-Inh complex levels were measured less frequently in serial samples from patients with septic shock than in those from patients without shock (P less than .0001). Based on these results, we conclude that plasma Cl(-)-Inh complex levels during sepsis may not properly reflect the extent of contact activation.