Serum concentrations of immunoreactive tumor necrosis factor/cachectin (TNF), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), and interferon-alpha (IFN alpha) were prospectively measured in 70 patients with septic shock to determine their evolution and prognostic values. In a univariate analysis, levels of TNF (P = .002) and IL-1 beta (P = .05) were associated with the patient's outcome, but not IFN alpha (P = .15) and IFN gamma (P = .26). In contrast, in a stepwise logistic regression analysis, the severity of the underlying disease (P = .01), the age of the patient (P = .02), the documentation of infection (nonbacteremic infections vs. bacteremias, P = .03), the urine output (P = .04), and the arterial pH (P = .05) contributed more significantly to prediction of patient outcome than the serum levels of TNF (P = .07). After 10 days, the median concentration of TNF was undetectable (less than 100 pg/ml) in the survivors, whereas it remained elevated (305 pg/ml, P = .002) in the nonsurvivors. Thus, in patients with septic shock due to various gram-negative bacteria, other parameters than the absolute serum concentration of immunoreactive TNF contributed significantly to the prediction of outcome.

The soluble glycoprotein sCD 14 binds lipopolysaccharide, a complex that activates endothelial cells and that may be crucial in gram-negative sepsis, Therefore, serum sCD14 was analyzed in 54 patients with gram-negative septic shock and in 26 healthy controls, sCD14 was tested by ELISA and Western blotting, Patients had higher sCD14 concentrations than controls (median, 3.23 vs. 2.48 #!g/mL, P = .002). Increased levels were associated with high mortality (median, 4.2 #Lg/mL in nonsurvivors vs. 2.8 #!g/mL in survivors, P = .001). sCD14 was found in two isoforms (49 and 55 kDa) in monocyte cultures. In sera only one of either form was detectable. Controls had the 49-kDa form, and patients had either the 49-or 55-kDa form, but patients with high levels of sCD14 had only the 55-kDa form. Twenty-one (53%) of 39 with the 55-kDa form and 8 (57%) of 14 with the 49-kDa form died. Thus, the level of sCD14 but not its biochemical form had a prognostic value in patients with gram-negative septic shock.Lipopolysaccharide (LPS) plays a key role in the pathophysiology of sepsis [I]. The LPS receptor on myeloid cells is the phosphatidylinositol-Iinked membrane glycoprotein CD 14 [2]. CD 14 occurs in a membrane-associated form and as a soluble (s) molecule [3,4]. sCD 14 is derived from the monocytic cell line Mono-Mac 6 in two forms [5]: A 48-kDa form is shed from the membrane of monocytes and MonoMac 6 cells [6,7], and a 56-kDa form is detectable in metabolically labeled Mono-Mac 6 cells and in sCD 14 purified from urine [3,5]. The serum concentration of sCD 14 is ,...., I millionfold higher than that ofcytokines [8]. Although much is known about cytokine liberation during experimental endotoxemia or sepsis, little is known about sCD 14 in these conditions [9][10][11][12]. Because CD 14 is the principle LPS receptor, the serum concentration ofsCD 14 may be modified during endotoxemia or sepsis. The physiologic role of sCD 14 is unknown. It could act as a scavenger by neutralizing circulating LPS [13] shown that complexes ofsCD 14 with LPS activate these cells [14,15].We measured sequential serum concentrations of sCD 14 in 54 patients with gram-negative septic shock, compared these with levels in normal controls, and correlated sCD 14 levels with patient outcome. We also determined the biochemical form of serum sCD 14 by Western blotting and compared it with sCD 14 derived from normal monocytes. MethodsPatients. The study population comprised 54 patients (33 males, 21 females) with documented gram-negative septic shock. Their median age was 58 years (range, 7-78). All were part of a previously described study that compared the efficacy of J5 hyperimmunoglobulin (n = 22) with standard intravenously (iv) administered IgG (n = 32) (Sandoglobulin; Sandoz Pharmaceuticals, Basel, Switzerland) [16]. The etiology ofseptic shock was established by the isolation of gram-negative bacteria from blood in 37 patients (69%). Of these, 30 had monomicrobial and 7 had polymicrobial bacteremia. Seventeen patients (3 t %) had documented gram-nega...

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