Cytokine dysregulation predicts mortality in malnourished children with septic shock: A prospective cohort study from Bangladesh

Abstract

Background

Septic shock in malnourished children carries mortality exceeding 70% in low-resource settings. While cytokine dysregulation is well-characterized in well-nourished septic children, data are lacking in malnourished children. Our objective was to characterize cytokine profiles and identify prognostic biomarkers in malnourished children with septic shock.

Methods

We prospectively enrolled children aged 1-59 months with moderate-to-severe malnutrition (weight-for-length or weight-for-age Z-score <-2) and septic shock (mean arterial pressure <50 mmHg) at icddr,b Dhaka Hospital ICU, Bangladesh. Baseline plasma samples were analyzed using multiplex immunoassay for nine cytokines: IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, IFN-γ, and GM-CSF. We compared concentrations between 28-day survivors and non-survivors using Wilcoxon rank-sum tests and assessed discrimination via ROC analysis. Multivariable logistic regression included IL-6, adjusting for age, sex, and malnutrition severity.

Results

Of 81 children (median age 6.6 months, 57% male), 61 (75%) died within 28 days. Non-survivors demonstrated significantly elevated inflammatory mediators: IL-6 (median 607 vs 46 pg/mL, p<0.001), IL-8 (1136 vs 503 pg/mL, p=0.009), IL-10 (397 vs 144 pg/mL, p=0.009), and TNF-α (257 vs 178 pg/mL, p=0.002). Non-survivors exhibited a markedly reduced IL-10/IL-6 ratio (0.9 vs 3.9, p=0.022), indicating inadequate anti-inflammatory counter-regulation. IL-6 demonstrated superior prognostic discrimination (AUC 0.76, 95% CI 0.65-0.88) compared to IL-8 (AUC 0.69, 95% CI 0.56-0.82). In multivariable analysis, IL-6 remained independently associated with mortality (adjusted OR 2.27, 95% CI 1.28-4.55, p=0.010).

Conclusions

Malnourished children with septic shock who died exhibited marked pro-inflammatory elevation with insufficient anti-inflammatory compensation, reflected by a low IL-10/IL6 ratio. IL-6 independently predicted mortality and may serve as a prognostic biomarker in this population. Our findings suggest immune dysregulation drives mortality, indicating future interventions should target immunologic dysfunction alongside conventional resuscitation strategies.

Bangladesh J Medicine 2026; Vol. 37, No. 2(1): pp. 222-223