Endotoxaemia and inflammatory mediators in febrile patients with haematological disease

To study the pattern of plasma levels of endotoxin, tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and C-reactive protein (CRP) in febrile neutropenic patients and to assess the potential diagnostic value of these analyses.

Consecutive prospective study.

Patients treated at the haematology ward at Danderyd Hospital, Sweden.

Ninety-four patients with fever and haematological disease entered the study (male/female: 59/35) with 176 febrile episodes.

Blood samples were drawn at days 0, 1, 2 and 6 after onset of fever for analysis of, endotoxin, TNF-alpha, IL-6 and CRP.

Infectious aetiology was established in 62.5% of the febrile episodes. Blood cultures showed significant growth in 71/176 (40.3%) febrile episodes. Nonbacteraemic bacterial infections were diagnosed in 34/176 (19.3%) episodes. Endotoxin was detected in plasma in 40% of febrile episodes regardless of aetiology. TNF-alpha was detected in 61% and IL-6 in 94% of all febrile episodes. The initial TNF-alpha and IL-6 levels were significantly higher in patients with Gram-negative bacteraemia than in patients with other causes of fever (P < 0.001). In episodes evaluated as successful after empirical antibiotic treatment, a significant (P < 0.001) decrease in CRP concentrations were found on day 6 after onset of fever.

The sustained, low-grade endotoxaemia and persistently elevated levels of TNF-alpha and IL-6 found in febrile patients may reflect a failing mucosal barrier that allows endogenous bacterial products to reach the circulation. The diagnostic value of endotoxin, TNF-alpha, IL-6 and CRP to discriminate between bacteraemic and nonbacteraemic febrile episodes was very limited. The study supports the present policy of broad, empirical antibiotic treatment in patients with haematological disease and fever.