title: Effects of heparin-binding protein (CAP37/azurocidin) in a porcine model of Actinobacillus pleuropneumoniae-induced pneumonia.
abstract: Heparin-binding protein (HBP; CAP37/azurocidin) is secreted from neutrophil leukocytes early during inflammation and plays a central role in early capillary leakage and extravasation of neutrophils. Furthermore, HBP is chemotactic towards monocytes and lymphocytes and protects against stress-induced apoptosis, e.g. induced by oxygen radicals released during inflammation. Thus, administration of HBP as an adjunct to antibiotics increased survival of mice with peritonitis. In the present study, the effects of recombinant HBP as an adjunct to standard antibiotics were examined in a porcine model of Actinobacillus pleuropneumoniae-induced pneumonia. Beneficial and possible adverse effects of HBP were evaluated clinically and pathologically as well as by measurement of clinical chemical variables and markers of inflammation (interleukin-6 and C-reactive protein) and oxidative stress (ascorbic acid and alpha-tocopherol). Pigs receiving HBP (0.55 mgkg-1, n=11) as a 6-hourly subcutaneous infusion starting 1-h post-infection had a faster decrease in rectal temperature compared to control animals receiving a carrier-infusion (n=11), with a significant lower temperature at 32 h post-infection (p<0.05). This difference was, however, transient and the temperature curves had a similar course from 38 h and onwards. The transient effect of HBP might be explained by the dosage regimen that was used. No signs of adverse effects of the HBP-infusion were observed. More studies are needed to elucidate of the effects of HBP further and to optimise the dosage regimen for further improvement the efficacy and safety.
authors.affiliation: Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, Copenhagen, Denmark. blz@novonordisk.com
authors.forename: Brian
authors.initials: B
authors.lastname: Lauritzen
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.forename: René
authors.initials: R
authors.lastname: Djurup
authors.forename: Hans
authors.initials: H
authors.lastname: Flodgaard
authors.forename: Ove
authors.initials: O
authors.lastname: Svendsen
mesh_terms: D000189:Actinobacillus Infections / Q000188:drug therapy* / Q000382:microbiology; D016977:Actinobacillus pleuropneumoniae / Q000187:drug effects*; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D007313:Insecta; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013552:Swine
chemical_list: C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D011994:Recombinant Proteins