ANTIINFLAMMATORY CYTOKINE PROFILE AND MORTALITY IN FEBRILE PATIENTS

Background An anti-inflammatory cytokine profile on whole-blood stimul ation in vitro is associated with fatal outcome of meningococcal disea se. We investigated whether an antiinflammatory cytokine profile in th e circulation is associated with adverse outcome in other infectious d iseases. Methods We enrolled 464 consecutive patients (272 men, 192 wo men) who presented to hospital with fever (greater than or equal to 38 .2 degrees C). On admission we measured plasma interleukin 10 (IL-10) and tumour necrosis factor alpha (TNF alpha), and collected clinical a nd microbiological data on the febrile illness, then followed up all p atients for clinical outcome. Findings In at least 399 of the 464 pati ents fever was caused by infection. 33 patients died after a median ho spital stay of 11 days (interquartile range 3-20). Concentrations of I L-10 were significantly higher in non-survivors (median 169 pg/mL [IQR 83-530]) than in survivors (median 88 pg/mL [42-235], p=0.042). When dichotomised around the median, the mortality risk was two times highe r in patients who had high concentrations of IL-10 than in those with low concentrations (relative risk 2.39 [95% CI 1.07-5.33]), in patient s with low and high concentrations of TNF alpha. In the 406 patients w ithout haemodynamic deterioration in the first 24 h, IL-10 was higher and TNF alpha lower in patients who died than in those who survived. T he ratio of IL-10 to TNF alpha was higher in non-survivors (median 6.9 [3.0-21.0]) than in survivors (median 3.9 [2.0-7.0], p=0.040). This r atio was highest in patients who died without underlying disease (medi an 21.5 [5.0-25.0]). Age, sex, and duration of fever before admission did not explain the differences in IL-10 and TNF alpha. Interpretation An anti-inflammatory cytokine profile of a high ratio of IL-10 to TNF alpha is associated with fatal outcome in febrile patients with commu nity-acquired infection. Our findings caution against a widespread use of proinflammatory cytokine inhibition in patients with sepsis.