The effect of corticotropin-release hormone on duodenal permeability and immune activation in healthy volunteers in a double-blind placebo-controlled study.
Level 2 - randomized trial
Randomized, double-blind, crossover trial in humans
PubMed 40167262 · doi:10.1152/ajpgi.00130.2024
What was done
Twenty healthy volunteers completed a double-blind, randomized crossover study evaluating the effect of an intravenous bolus of 100-µg corticotropin-releasing hormone (CRH) versus placebo. Two hours post-injection, subjects underwent gastroscopy to obtain duodenal biopsies for measuring mucosal permeability in Ussing chambers, quantifying mast cells and eosinophils, and assaying biopsy supernatant for tryptase, chymase, and eosinophil-derived neurotoxin (EDN). In parallel, baseline biopsies were exposed to CRH ex vivo with or without the mast cell stabilizer lodoxamide to measure transepithelial electrical resistance (TEER).
What was found
In vivo CRH did not significantly alter duodenal mast cell counts (P = 0.31) or eosinophil counts (P = 0.069) compared to placebo, and duodenal permeability was unchanged. Biopsy supernatant tryptase significantly decreased after in vivo CRH compared to placebo (P = 0.037), while chymase did not change (P = 0.44) and EDN showed a non-significant decreasing trend (P = 0.053). In contrast, ex vivo exposure of baseline biopsies to CRH significantly decreased TEER (increased permeability) compared to baseline (P = 0.010), an effect that was not prevented by lodoxamide pretreatment.
Why it matters
The study demonstrates a divergence between direct local tissue effects of CRH and systemic in vivo administration on duodenal mucosal integrity, suggesting systemic compensatory mechanisms in healthy humans that prevent stress-hormone-induced barrier disruption.
Limits
The sample size was small (20 subjects), restricted solely to healthy volunteers, and evaluated only a single intravenous dose of CRH at one 2-hour time point, precluding direct generalizability to functional dyspepsia patients or chronic stress states. Specific numerical values for permeability metrics and cell counts were omitted from the abstract.
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