van Dissel J T, van Langevelde P, Westendorp R G, Kwappenberg K, Frölich M
Department of Infectious Diseases, Leiden University Medical Centre, The Netherlands.
Lancet. 1998 Mar 28;351(9107):950-3. doi: 10.1016/S0140-6736(05)60606-X.
An anti-inflammatory cytokine profile on whole-blood stimulation in vitro is associated with fatal outcome of meningococcal disease. We investigated whether an anti-inflammatory cytokine profile in the circulation is associated with adverse outcome in other infectious diseases.
We enrolled 464 consecutive patients (272 men, 192 women) who presented to hospital with fever (> or = 38.2 degrees C). On admission we measured plasma interleukin 10 (IL-10) and tumour necrosis factor alpha (TNF alpha), and collected clinical and microbiological data on the febrile illness, then followed up all patients for clinical outcome.
In at least 399 of the 464 patients fever was caused by infection. 33 patients died after a median hospital stay of 11 days (interquartile range 3-20). Concentrations of IL-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 higher 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 patients with low and high concentrations of TNF alpha. In the 406 patients without haemodynamic deterioration in the first 24 h, IL-10 was higher and TNF alpha lower in patients who died than in those who survived. The 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 ratio was highest in patients who died without underlying disease (median 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.
An anti-inflammatory cytokine profile of a high ratio of IL-10 to TNF alpha is associated with fatal outcome in febrile patients with community-acquired infection. Our findings caution against a widespread use of proinflammatory cytokine inhibition in patients with sepsis.
体外全血刺激时的抗炎细胞因子谱与脑膜炎球菌病的致命结局相关。我们调查了循环中的抗炎细胞因子谱是否与其他传染病的不良结局相关。
我们纳入了464例连续入院的发热（体温≥38.2℃）患者（男性272例，女性192例）。入院时我们检测了血浆白细胞介素10（IL-10）和肿瘤坏死因子α（TNFα），并收集了发热性疾病的临床和微生物学数据，随后对所有患者的临床结局进行随访。
464例患者中至少399例发热由感染引起。33例患者在中位住院11天（四分位间距3 - 20天）后死亡。非幸存者的IL-10浓度（中位数169 pg/mL [四分位间距83 - 530]）显著高于幸存者（中位数88 pg/mL [42 - 235]，p = 0.042）。以中位数为界进行二分法分析时，IL-10浓度高的患者的死亡风险是浓度低的患者的两倍（相对风险2.39 [95%可信区间1.07 - 5.33]），TNFα浓度低和高的患者情况相同。在最初24小时内无血流动力学恶化的406例患者中，死亡患者的IL-10较高而TNFα较低。非幸存者的IL-10与TNFα之比（中位数6.9 [3.0 - 21.0]）高于幸存者（中位数3.9 [2.0 - 7.0]，p = 0.040）。该比值在无基础疾病的死亡患者中最高（中位数21.5 [5.0 - 25.0]）。年龄、性别和入院前发热持续时间无法解释IL-10和TNFα的差异。
IL-10与TNFα比例高的抗炎细胞因子谱与社区获得性感染发热患者的致命结局相关。我们的研究结果警示不要在脓毒症患者中广泛使用促炎细胞因子抑制措施。
