title: Reduced physeal area and chondrocyte proliferation in Pasteurella multocida toxin-treated rats.
abstract: Pasteurella multocida toxin depresses weight gain in rats and pigs. It also affects tissues with rapidly dividing cells. In the present study, we investigated the role of this protein toxin on chondrocyte growth in vivo. Rats were divided into a single- or multiple-dose group and were given, respectively, either a single injection (0.15 or 0.6 micrograms/kg toxin subcutaneously) or multiple injections (0.01-0.2 micrograms/kg subcutaneously) of toxin. Bone (humerus) and other selected tissues were stained for bromodeoxyuridine immunoreactivity (BrDU-IR) in order to gauge cell proliferation. Physeal area was measured in rats from the multiple-dose group. Serum from single- and multiple-dose groups were tested for tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) activity using a bioassay system. Decreased weight gain, feed intake, and feed efficiency were observed in single- and multiple-dose groups of rats. Decreased BrDU-IR indices were present in the resting and proliferative zone chondrocytes of the humeral physis in rats from the multiple-dose group, as was decreased physeal area. Increased serum IL-6 bioactivity was present in rats after 24 hours, and no changes in TNF-alpha bioactivity were seen in any group. No alterations in BrDU-IR were seen in rats fed restricted (80% of control) diets. These studies show that sublethal doses of toxin decrease weight gain and affect growth of long bones through suppression of chondrocyte proliferation. These effects may be mediated by direct binding of the toxin to target cells or IL-6 but are not associated with altered feed intake or TNF-induced cachexia.
authors.affiliation: National Animal Disease Center, Ames, IA, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Ackermann
authors.forename: J R
authors.initials: JR
authors.lastname: Stabel
authors.forename: R K
authors.initials: RK
authors.lastname: Pettit
authors.forename: C D
authors.initials: CD
authors.lastname: Jacobson
authors.forename: J K
authors.initials: JK
authors.lastname: Elmquist
authors.forename: K B
authors.initials: KB
authors.lastname: Register
authors.forename: R B
authors.initials: RB
authors.lastname: Rimler
authors.forename: J H
authors.initials: JH
authors.lastname: Hilton
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000032:analysis / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006132:Growth Plate / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006811:Humerus; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology; D007457:Iodine Radioisotopes; D008099:Liver / Q000737:chemistry / Q000166:cytology; D008297:Male; D016979:Pasteurella multocida; D051381:Rats; D013737:Testis / Q000737:chemistry / Q000166:cytology; D013950:Thymus Gland / Q000737:chemistry / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015850:Interleukin-6; D007457:Iodine Radioisotopes; C062258:Pasteurella multocida toxin; D014409:Tumor Necrosis Factor-alpha