P Brandtzæg

Serum samples from patients with meningococcal disease were examined for the presence of IL-6, TNF-alpha, and LPS. Median serum concentration of IL-6 was 1,000 times higher in patients with septic shock (189 ng/ml) than in patients with bacteriaemia, meningitis, or combined septic shock and meningitis. 11 of 21 patients with serum levels greater than 3.0 ng/ml died, whereas all 58 patients with serum levels at less than or equal to 3.0 ng/ml, survived. All four patients with serum IL-6 levels greater than 750 ng/ml, died. IL-1 was detected in serum from three patients who also had high serum levels of IL-6, TNF-alpha, and LPS, and rapidly fatal courses. IL-6 appeared to be released into serum later than TNF-alpha, and was detected in serum for up to 36 h. The half-life of IL-6 and TNF-alpha was calculated to be 103 +/- 27 min and 70 +/- 11 min, respectively. These data indicate that a complex pattern of cytokines exists in serum from patients with meningococcal septic shock, and that the release of IL-6 and IL-1, in addition to TNF-alpha, is associated with fatal outcome.

We studied prospectively the quantitative relation of circulating endotoxin (lipooligosaccharides [LOSs]) and the development of multiple organ failure and death in 45 consecutively admitted patients with bacteriologically verified systemic meningococcal disease (SMD). A plasma LOS level of greater than 700 ng/L correlated with development of severe septic shock (P less than .0001), adult respiratory distress syndrome (P = .0035), a pathologically elevated serum creatinine level (P less than .0001), or death as a consequence of multiple organ failure (P = .0002). Initial plasma LOS levels of less than 25, 25-700, 700-10,000, and greater than 10,000 ng/L were associated with 0%, 14%, 27%, and 86% fatality, respectively. The LOS half-life after initiation of antibiotic therapy was 1-3 h. Increasing plasma LOS levels were never seen. These observations suggest that LOS quantitation using the limulus amebocyte lysate assay with a chromogenic substrate gives important progsnotic information and may provide new insight concerning pathophysiological aspects of SMD.