Children With Noncritical Infections Have Increased Intestinal Permeability, Endotoxemia and Altered Innate Immune Responses

BACKGROUND: Children with critical illness have increased intestinal permeability and a period of immunoparalysis, mediated by elevated circulating endotoxin. Whether children with less severe infections have similar changes is uncertain. METHODS: We conducted a proof-of-concept pilot study, enrolling children 6-59 months of age hospitalized for noncritical infections (cases, n = 11) and noninfected controls (n = 19). Intestinal permeability was measured by lactulose-mannitol recovery. Plasma endotoxin, blood monocyte and neutrophil immunophenotypes and cytokine elaboration following 24-hour whole-blood culture with antigens targeting distinct innate pathogen recognition receptor signaling pathways were evaluated. RESULTS: Cases had higher intestinal permeability and plasma endotoxin levels than controls. Among cases versus controls, fewer monocytes expressed human leukocyte antigen DR isotype (HLA-DR) (87.1% vs. 96.4%, P = 0.001), and more expressed CD64 (99.6% vs. 97.6%, P = 0.041). Following zymosan stimulation of whole blood, cases versus controls produced less interleukin 1 beta (IL-1β) (median 1101 vs. 2604 pg/mL, P = 0.048) and tumor necrosis factor alpha (TNF-α) (2342 vs. 5130 pg/mL, P = 0.031). Children with higher (≥0.1 endotoxin unit (EU)/mL) versus lower (