The level of endotoxemia in sepsis varies in relation to the underlying infection: Impact on final outcome

• Among patients with sepsis, endotoxemia is greater after community-acquired pneumonia and primary bacteremia.
• Circulating LPS decrease within the first 48 h in survivors.
• Circulating monocytes from patients with significant endotoxemia become hyporesponsive to ex vivo stimulation.

Former studies of our group have shown that the innate and adaptive immune status may differ in relation with the causative infection. To this same end, it was investigated if kinetics of circulating lipopolysaccharide (LPS) leading to inflammatory response may differ. Blood was sampled from 189 patients with sepsis and 206 with severe sepsis/shock starting 24 h from advent of sepsis and repeating on day 3. Serum LPS was measured by Limulus Amebocyte Lysate (LAL) assay. From 59 patients, circulating monocytes were isolated and incubated in the absence/presence of LPS. Concentrations of tumor necrosis factor-alpha (TNFα) were measured in supernatants by an enzyme immunoassay. In either category of severity, circulating LPS was greater among sufferers from primary Gram-negative bacteremia (BSI) and from community-acquired pneumonia (CAP) than sufferers from other underlying infections. LPS were greater among patients with BSI compared to patients with secondary Gram-negative bacteremia and patients without bacteremia. Greater decrease of circulating LPS over 48 h was recorded for survivors compared to non-survivors only within sufferers from BSI and CAP. Significant endotoxemia was considered for patients with serum LPS within the upper quartile of distribution; their monocytes were less potent for release of TNFα. It is concluded that endotoxemia in sepsis varies greatly with the underlying infection; this is related with immunoparalysis of monocytes with implications on final outcome.