title: Effects of anti-inflammatory agents on serum levels of calcitonin precursors during human experimental endotoxemia.
abstract: 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.
authors.affiliation: Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Preas
authors.forename: E S
authors.initials: ES
authors.lastname: Nylen
authors.forename: R H
authors.initials: RH
authors.lastname: Snider
authors.forename: K L
authors.initials: KL
authors.lastname: Becker
authors.forename: J C
authors.initials: JC
authors.lastname: White
authors.forename: J M
authors.initials: JM
authors.lastname: Agosti
authors.forename: A F
authors.initials: AF
authors.lastname: Suffredini
mesh_terms: 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
chemical_list: 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