Evaluation of Effect of Probiotics on Cytokine Levels in Critically Ill. (Newman)

Angurana SK, et al. Evaluation of Effect of Probiotics on Cytokine Levels in Critically Ill Children With Severe Sepsis: A Double-Blind, Placebo-Controlled Trial. Crit Care Med. 2018 Oct;46(10):1656-1664.

OBJECTIVES: To evaluate the effect of probiotics on cytokines in children with severe sepsis.

DESIGN: Randomized, double-blind, placebo-controlled trial.

SETTING: ICU of a tertiary care teaching hospital in North India.

PATIENTS: Children 3 months to 12 years old with severe sepsis.

INTERVENTIONS: 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.

MEASUREMENTS AND MAIN RESULTS: 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.

CONCLUSIONS: Probiotics supplementation for 7 days resulted in significant decrease in proinflammatory and increase in antiinflammatory cytokines in children with severe sepsis.

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