Endotoxin induces an exaggerated interleukin-10 response in peritoneal macrophages of children compared with adults

Area of Science:

• Immunology
• Pediatric Medicine
• Trauma Research

Background:

• Children exhibit lower rates of multiple organ failure (MOF) post-injury compared to adults.
• MOF is linked to systemic hyperinflammation, suggesting age-related differences in inflammatory responses.
• Investigating these differences in peritoneal macrophages (PMs) is crucial for understanding pediatric trauma outcomes.

Purpose of the Study:

• To compare the lipopolysaccharide (LPS)-induced pro- and anti-inflammatory cytokine response of pediatric versus adult peritoneal macrophages (PMs).
• To test the hypothesis that pediatric PMs exhibit an enhanced anti-inflammatory response compared to adult PMs.

Main Methods:

• Human peritoneal macrophages (PMs) were isolated from pediatric (n=9, mean age 5.4 years) and adult (n=8, mean age 41.6 years) cohorts.
• PMs were stimulated with lipopolysaccharide (LPS) to assess cytokine production.
• Statistical significance was set at P < 0.05.

Main Results:

• LPS stimulation induced a 50-fold increase in interleukin-10 (IL-10) production in pediatric PMs compared to adults.
• Tumor necrosis factor-alpha (TNF-alpha) production was also elevated in pediatric PMs post-LPS stimulation.
• The ratio of anti-inflammatory (IL-10) to pro-inflammatory (TNF-alpha) cytokines was 20-fold higher in pediatric versus adult PMs.

Conclusions:

• Pediatric peritoneal macrophages demonstrate increased production of both IL-10 and TNF-alpha in response to LPS.
• The anti-inflammatory to pro-inflammatory cytokine ratio is significantly higher in children, indicating a distinct immune response.
• These findings suggest age-dependent differences in the cytokine balance within resident macrophages, impacting inflammatory responses to injury.