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Updated: Aug 20, 2026
Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
p38-MAPK inhibition and endotoxin induced tubular dysfunction in men
Jan G Zijlstra1, Jaap E Tulleken, Jack J M Ligtenberg
1Intensive and Respiratory Care Unit, Department of Internal Medicine, University Hospital Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Background:
To evaluate the possibility of preventing endotoxin induced renal damage by p38-MAPK inhibition in a human model.
Design And Methods:
Twenty-one healthy young male volunteers received 4 ng/kg Escherichia coli endotoxin as a single dose. Four groups of volunteers received an oral dose of placebo or 350, 700 or 1400 mg RWJ-67657, a p38-MAPK inhibitor, 20 min before endotoxin infusion. Urine samples were collected at set time intervals. The urinary excretion rate of beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase, as indicators of tubular dysfunction was determined.
Results:
There was a significant increase of beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase urine excretion rate after endotoxin infusion in the placebo group. p38-MAPK inhibition prevented the increase of markers for tubulopathy.
Conclusions:
Endotoxin infusion induces measurable tubular damage. Blocking the p38-MAPK may prevent this damage. The mechanism is unclear, but blocking TNF-alpha release is a possible explanation.
