Lauterbach R, Zembala M
Department of Clinical Immunology, Jagiellonian University Medical College, Cracow, Poland.
Eur J Pediatr. 1996 May;155(5):404-9. doi: 10.1007/BF01955273.
Increased plasma tumour necrosis factor alpha (TNF) concentration correlates with mortality in sepsis. We suggested that pentoxifylline (PTXF), which is known to inhibit TNF production, may improve survival and attenuate clinical symptoms of sepsis in neonates. Plasma TNF levels were evaluated in 29 newborn infants with sepsis. Patients were randomly assigned into two groups, receiving PTXF in a dose of 5 mg/kg per hour for 6 h or placebo (saline), on 3 successive days. Both groups were subjected to the same conventional therapy. TNF was evaluated before and after PTXF or placebo administration on the 1st and 3rd days of therapy. There was a statistically significant decrease in plasma TNF level in the PTXF group when the values before the first and after the last PTXF infusion were compared [mean: 671.5 pg/ml; SD: 438; med: 729.6 vs mean: 41.0 pg/ml; SD: 64.1; med: 11.5; P < 0.000004]. In the placebo group, decrease was not significant [mean: 633.0 pg/ml SD: 488.6; med: 618.9 vs 246.9 pg/ml; SD: 243.9; med: 191.0]. A significantly higher plasma TNF level, evaluated after the last PTXF infusion, was found in the placebo group [246.9 pg/ml vs 41.0 pg/ml; P < 0.001]. Only one of four infants with signs of shock in the placebo group survived, whereas all of five newborns with symptoms of shock in the PTXF group survived [P < 0.04]. An increased incidence of metabolic acidosis [P < 0.05], necrotizing enterocolitis [P < 0.04] and renal insufficiency [P < 0.05] was observed in infants in the placebo group.
PTXF inhibits production of TNF and may have therapeutic value in the treatment of premature infants with sepsis complicated by shock.
脓毒症患者血浆肿瘤坏死因子α（TNF）浓度升高与死亡率相关。我们推测，已知可抑制TNF产生的己酮可可碱（PTXF）可能会提高新生儿脓毒症的生存率并减轻其临床症状。对29例脓毒症新生儿的血浆TNF水平进行了评估。患者被随机分为两组，连续3天接受每小时5mg/kg剂量的PTXF治疗6小时或接受安慰剂（生理盐水）治疗。两组均接受相同的常规治疗。在治疗的第1天和第3天，在给予PTXF或安慰剂之前和之后评估TNF。比较首次PTXF输注前和最后一次PTXF输注后的血浆TNF水平，PTXF组有统计学显著下降[平均值：671.5pg/ml；标准差：438；中位数：729.6 vs平均值：41.0pg/ml；标准差：64.1；中位数：11.5；P<0.000004]。在安慰剂组中，下降不显著[平均值：633.0pg/ml标准差：488.6；中位数：618.9 vs 246.9pg/ml；标准差：243.9；中位数：191.0]。在安慰剂组中，最后一次PTXF输注后评估的血浆TNF水平显著更高[246.9pg/ml vs 41.0pg/ml；P<0.001]。安慰剂组中四名有休克体征的婴儿中只有一名存活，而PTXF组中五名有休克症状的新生儿全部存活[P<0.04]。在安慰剂组的婴儿中观察到代谢性酸中毒[P<0.05]、坏死性小肠结肠炎[P<0.04]和肾功能不全[P<0.05]的发生率增加。
PTXF可抑制TNF的产生，对治疗并发休克的脓毒症早产儿可能具有治疗价值。
