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 inflammation. The duration of their elevation after intravenous endotoxin challenge and the effects of anti-inflammatory therapies were studied in 52 subjects. 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, CTpr 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 ibuprofen (compared with endotoxin alone) increased CTpr levels approximately 2-fold (P=.03), whereas soluble tumor necrosis factor receptor blunted the increase in CTpr levels by 2-3-fold (P=.0015). However, soluble interleukin-1 receptor failed to alter the increase in CTpr levels. Thus, the fact that anti-inflammatory agents may alter CTpr levels resulting from a single stimulus must be considered when CTpr is used as a clinical marker. Of importance, this study reveals that anti-inflammatory agents may modulate the CTpr level, which is a potential toxic mediator of inflammation.
Preas
H L
HL
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Nylen
E S
ES
Snider
R H
RH
Becker
K L
KL
White
J C
JC
Agosti
J M
JM
Suffredini
A F
AF
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002116:Calcitonin / Q000097:blood*; D019446:Endotoxemia / Q000097:blood* / Q000503:physiopathology; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity; D004926:Escherichia coli; D000068800:Etanercept; D005260:Female; D006207:Half-Life; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000494:pharmacology; D007249:Inflammation; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011498:Protein Precursors / Q000097:blood*; D011863:Radioimmunoassay; D018124:Receptors, Tumor Necrosis Factor
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D004731:Endotoxins; D007074:Immunoglobulin G; D010919:Placebos; D011498:Protein Precursors; D018124:Receptors, Tumor Necrosis Factor; D002116:Calcitonin; D002097:C-Reactive Protein; D000068800:Etanercept; D007052:Ibuprofen