Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Department of Pediatrics, Medanta, The Medicity, Gurugram, NCR, India.
Crit Care Med. 2018 Oct;46(10):1656-1664. doi: 10.1097/CCM.0000000000003279.
To evaluate the effect of probiotics on cytokines in children with severe sepsis.
Randomized, double-blind, placebo-controlled trial.
ICU of a tertiary care teaching hospital in North India.
Children 3 months to 12 years old with severe sepsis.
Enrolled children were randomized to probiotic (n = 50) and placebo (n = 50) groups. Probiotic group received VSL#3 (Danisco-Dupont USA, Madison, WI) (Lactobacillus paracasei, L. plantarum, L. acidophilus, L. delbrueckii, Bifidobacterium longum, B. infantis, B. breve, Streptococcus salivarius; maltose and silicon dioxide), and placebo group received maltose and silicon dioxide. Dose was 1 sachet twice daily for 7 days. Blood was collected on days 1 and 7 for estimation of interleukin-6, interleukin-12p70, interleukin-17, tumor necrosis factor-α, interleukin-10, and transforming growth factor -β1. "Primary outcome": Change in cytokine levels in probiotic and placebo groups from day 1 to 7. "Secondary outcomes": Sequential Organ Failure Assessment score, healthcare-associated infections, ICU stay, and mortality.
On day 7, probiotic group had significantly lower levels of proinflammatory cytokines (interleukin-6 [80 vs 186 pg/mL, p = 0.001]; interleukin-12p70 [44 vs 79 pg/mL, p = 0.001]; interleukin-17 [217 vs 293 pg/mL, p = 0.01]; and tumor necrosis factor-α [192 vs 348 pg/mL, p = 0.01]) and higher levels of antiinflammatory cytokines (interleukin-10 [320 vs 240 pg/mL, p = 0.02] and transforming growth factor-β1 [311 vs 221 ng/mL, p = 0.01]) than placebo group. From day 1 to 7, probiotic group showed significant decrease in proinflammatory cytokines (interleukin-6 [196-80 pg/mL, p = 0.001]; interleukin-12p70 [71-44 pg/mL, p = 0.01]; interleukin-17 [258-217 pg/mL, p = 0.01]; and tumor necrosis factor-α [347-192 pg/mL, p = 0.001]) and increase in antiinflammatory cytokines (interleukin-10 [198-320 pg/mL, p = 0.001] and transforming growth factor-β1 [216-311 ng/mL, p = 0.001]) as compared to placebo group. Sequential Organ Failure Assessment score on day 7 was significantly less in probiotic group (1 vs 3). There was a nonsignificant trend toward lower incidence of healthcare-associated infections (14% vs 20%) and duration of ICU stay (6.5 vs 9 d) in probiotic group. Mortality was similar in two groups.
Probiotics supplementation for 7 days resulted in significant decrease in proinflammatory and increase in antiinflammatory cytokines in children with severe sepsis.
评估益生菌对严重脓毒症患儿细胞因子的影响。
随机、双盲、安慰剂对照试验。
印度北部一家三级教学医院的 ICU。
3 个月至 12 岁的严重脓毒症患儿。
入组患儿随机分为益生菌（n = 50）和安慰剂（n = 50）组。益生菌组接受 VSL#3（Danisco-Dupont USA，Madison，WI）（鼠李糖乳杆菌、植物乳杆菌、嗜酸乳杆菌、德氏乳杆菌保加利亚亚种、长双歧杆菌、婴儿双歧杆菌、短双歧杆菌、唾液链球菌；麦芽糖和二氧化硅），安慰剂组接受麦芽糖和二氧化硅。剂量为每天 2 次，每次 1 包，共 7 天。于第 1 天和第 7 天采血，用于测定白细胞介素-6、白细胞介素-12p70、白细胞介素-17、肿瘤坏死因子-α、白细胞介素-10 和转化生长因子-β1。“主要结局”：益生菌和安慰剂组从第 1 天到第 7 天细胞因子水平的变化。“次要结局”：序贯器官衰竭评估评分、医疗保健相关感染、ICU 住院时间和死亡率。
第 7 天，益生菌组促炎细胞因子水平显著降低（白细胞介素-6[80 比 186 pg/mL，p = 0.001]；白细胞介素-12p70[44 比 79 pg/mL，p = 0.001]；白细胞介素-17[217 比 293 pg/mL，p = 0.01]；肿瘤坏死因子-α[192 比 348 pg/mL，p = 0.01]），抗炎细胞因子水平显著升高（白细胞介素-10[320 比 240 pg/mL，p = 0.02]和转化生长因子-β1[311 比 221 ng/mL，p = 0.01]），而安慰剂组。从第 1 天到第 7 天，益生菌组促炎细胞因子显著减少（白细胞介素-6[196-80 pg/mL，p = 0.001]；白细胞介素-12p70[71-44 pg/mL，p = 0.01]；白细胞介素-17[258-217 pg/mL，p = 0.01]；肿瘤坏死因子-α[347-192 pg/mL，p = 0.001]），抗炎细胞因子增加（白细胞介素-10[198-320 pg/mL，p = 0.001]和转化生长因子-β1[216-311 ng/mL，p = 0.001]），与安慰剂组相比。第 7 天的序贯器官衰竭评估评分明显较低（1 比 3）。益生菌组的医疗保健相关感染发生率（14%比 20%）和 ICU 住院时间（6.5 比 9 d）呈下降趋势，但无统计学意义。两组死亡率相似。
益生菌补充治疗 7 天可显著降低严重脓毒症患儿的促炎细胞因子水平，增加抗炎细胞因子水平。
