C1-esterase inhibitor infusion increases survival rates for patients with sepsis*.

OBJECTIVES: Systemic inflammatory response variability displays differing degrees of organ damage and differing outcomes of sepsis. C1-esterase inhibitor, an endogenous acute-phase protein, regulates various inflammatory and anti-inflammatory pathways, including the kallikrein-kinin system and leukocyte activity. This study assesses the influence of high-dose C1-esterase inhibitor administration on systemic inflammatory response and survival in patients with sepsis. DESIGN: Open-label randomized controlled study. SETTING: Surgical and medical intensive care units of nine university and city hospitals. PATIENTS: : Sixty-one patients with sepsis. INTERVENTIONS: Patients were randomized to receive either 12,000 U of C1-esterase inhibitor infusions in addition to conventional treatment or conventional treatment only (n = 41 C1-esterase inhibitor, 20 controls). Blood samples for measurement of C1-esterase inhibitor, complement components C3 and C4, and C-reactive protein concentrations were drawn on days 1, 3, 5, 7, 10, and 28. MEASUREMENTS AND MAIN RESULTS: Quartile analysis of C1-esterase inhibitor activity in sepsis subjects revealed that the lowest quartile subgroup had similar activity levels (0.7-1.2 U/L), when compared to healthy volunteers (p > .05). These normal-level C1-esterase inhibitor sepsis patients nevertheless displayed increased C-reactive protein (p = .04) production and higher likelihoods of a more severe sepsis (p = .001). Overall, infusion of C1-esterase inhibitor increased C1-esterase inhibitor (p < .005 vs. control on days 2, 3, and 5) functional activity, resulted in higher C3 levels (p < .05 vs. control on days 2 and 3), followed by decreased C-reactive protein (p < .05 vs. control on days 3 and 10). Simultaneously, C1-esterase inhibitor infusion in sepsis patients was associated with reduced all-cause mortality (12% vs. 45% in control, p = .008) as well as sepsis-related mortality (8% vs. 45% in control, p = .001) assessed over 28 days. The highest absolute reduction risk of 70% was achieved in sepsis patients with Simplified Acute Physiology Score II scores >27. CONCLUSION: In the present study, patients in the lowest quartile of C1-esterase inhibitor activity in combination with high C-reactive protein demonstrated a higher risk of developing severe sepsis. In general, high-dose C1-esterase inhibitor infusion down-regulated the systemic inflammatory response and was associated with improved survival rates in sepsis patients, which could have important treatment and survival implications for individuals with C1-esterase inhibitor functional deficiency.

Circulating cytokines as markers of systemic inflammatory response in severe community-acquired pneumonia.

OBJECTIVES: To assess the influence of empirical antibacterial therapy on systemic inflammatory response in patients with severe community-acquired pneumonia (CAP). MATERIAL AND METHODS: Thirty consecutive patients with CAP meeting systemic inflammatory response syndrome (SIRS) criteria were recruited into this study. Blood samples for measurement of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and C-reactive protein (CRP) concentrations were drawn on days 1, 3, 5, 7 and 10. For analysis, these patients were divided into two subgroups according to British Thoracic Society (BTS) severity score and to clinical response to the initial antibacterial therapy. RESULTS: In the group with severe CAP (n= 15), serum concentrations of IL-6 (P = 0.0001), IL-8, (P = 0.001), IL-10 (P = 0.0001) and CRP (P = 0.0001) were significantly higher compared to patients from the non-severe group (n= 15). IL-6 presented with a sharp decrease between days 1 and 3 in non-responders with severe CAP (P = 0.004). IL-6 concentrations on day 1 were significantly associated with a response to empirical antibacterial treatment by day 3. CONCLUSION: Despite the absence of a clinical response to empirical antibacterial treatment as assessed by conventional clinical parameters on day 3 in patients with severe CAP meeting SIRS criteria, there was a marked reduction in the degree of the systemic inflammatory response as reflected by IL-6 levels.