Effects of anti-inflammatory agents on serum levels of calcitonin precursors during human experimental endotoxemia

Calcitonin precursor (CTpr) levels are both markers and mediators of inflam mation. The duration of their elevation after intravenous endotoxin challen ge and the effects of anti-inflammatory therapies were studied in 52 subjec ts. CTpr levels maximized at 24 h in all subjects. At 7 days (n = 4), after levels of acute-phase cytokines and C-reactive protein had normalized, CTp r levels remained 2-4-fold above baseline levels. The elimination half-life of CTpr levels ranged from 26.9 to 45.7 h. At 24 h, endotoxin and ibuprofe n (compared with endotoxin alone) increased CTpr levels similar to2-fold (P = .03), whereas soluble tumor necrosis factor receptor blunted the increas e in CTpr levels by 2-3-fold (P = .0015). However, soluble interleukin-1 re ceptor failed to alter the increase in CTpr levels. Thus, the fact that ant i-inflammatory agents may alter CTpr levels resulting from a single stimulu s must be considered when CTpr is used as a clinical marker. Of importance, this study reveals that anti-inflammatory agents may modulate the CTpr lev el, which is a potential toxic mediator of inflammation.