Correlation of cytokine levels with clinical markers of organ hypoperfusion in sepsis syndrome patients (INTERSEPT trial)

The consequences of severe sepsis syndrome and septic shock include inadequate perfusion of organs and eventually organ failure. Organ hypoperfusion results in anaerobic glucose metabolism, metabolic acidosis and a predominant eatabolic state. The baseline levels of cytokines such as TNF and IL6 correlate with the number of organ hypoperfusions and with well known clinical laboratory markers for these metabolic changes.

Five hundred and fifty-three patients (pts) with sepsis syndrome were treated with a 30 min infusion of 3 or 15 mg/kg of a murine monoclonal antibody to human TNF or placebo. Plasma levels of 504 pts prior to infusion (baseline) and 1 h after infusion were analysed for TNF (ELISA) and 1L6 (B9¹ bioassay). At baseline there was a significant correlation between cytokine levels, particularly IL6, and the number of organ hypoperfusions (TNF: 55.0 pg/ml for I organ hypoperfusion to 100.0 pg/ml for 5 organ hypoperfusions, P = 0.0002; IL6: 1.69 ng/ml for I organ hypoperfusion to 25.02 ng/ml for 5 organ hypoperfusions, P < 0.0001). Likewise, the number of organs failing (range from 0 to 5) prior to infusion was significantly correlated with either cytokine (TNF: P = 0.0072; IL6: P = 0.0032: Kruskal-Wallis). The baseline levels of TNF and/or IL6 were also significantly correlated with arterial blood pH (TNF: r =-0.0709. P = 0.1715: IL6: r= -0.1966, P < 0.0001), plasma lactate (TNF: r = 0.3861, P < 0.0001; IL6: r = 0.3984, P < 0.0001), total serum protein/albumin (TNF: r = -0.1073. P = 0.0544; IL6: r = -0.1642, P = 0.0031) or urea (TNF: r = 0.2517, P < 0.0001; IL6: r = 0.0561, P = 0.2815), as well as with laboratory markers for renal failure and DIC such as serum creatinine (TNF: r = 0.3716, P < 0.0001: IL6: r = 0.1903. P = 0.0002), partial thromboplastin time (PTT) (TNF: r = 0.2042. P = 0.0001; IL6: r = 0.2940, P < 0.0001) and platelet count (TNF: r = -0.2777, P < 0.0001: IL6: r =-0.2190, P < 0.0001).