title: Local expression of tumor necrosis factor alpha in an experimental model of acute osteomyelitis in rats.
abstract: The inflammatory response associated with Staphylococcus aureus osteomyelitis results in extensive bone damage characterized by apparent increases in bone resorption and formation. These results suggest an increased local release of agents capable of modulating bone remodelling. Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine proposed to play an important role both in normal bone remodelling and in bone diseases; however, its potential role in osteomyelitis is unclear. This study evaluated changes in bone TNF levels during infection, using a rat model of acute osteomyelitis due to S. aureus. Following direct tibial infection, bacterial counts in bone were persistently high (approximately 6 log10 CFU/g of bone over 63 days) and bone weights increased. TNF activity was undetectable in uninfected bone (<0.01 ng/g of bone) but dramatically higher in infected bone (up to 5.2 +/- 3.5 ng/g of bone). Although TNF-alpha mRNA was weakly detected in uninfected bone, osteomyelitis was associated with up to 37-fold increases in expression of both the 1.6- and 2.4-kb transcripts. Both TNF activity and mRNA transcript levels remained elevated throughout the course of infection. TNF-alpha mRNA detected by in situ hybridization was present in osteoblasts as well as in populations of marrow cells and/or inflammatory infiltrate cells. Histopathology of infected bone indicated extensive bone resorption and adjacent areas of formation that were associated with cells expressing TNF-alpha mRNA. These data suggest that the elevated TNF levels induced by experimental infection may be directly related to changes in the histology of bone during osteomyelitis.
authors.affiliation: Novartis Pharma, Inc., Basel, Switzerland.
authors.forename: A J
authors.initials: AJ
authors.lastname: Littlewood-Evans
authors.forename: M R
authors.initials: MR
authors.lastname: Hattenberger
authors.forename: C
authors.initials: C
authors.lastname: Lüscher
authors.forename: A
authors.initials: A
authors.lastname: Pataki
authors.forename: O
authors.initials: O
authors.lastname: Zak
authors.forename: T
authors.initials: T
authors.lastname: O'Reilly
mesh_terms: D000208:Acute Disease; D000818:Animals; D001842:Bone and Bones / Q000473:pathology; D017403:In Situ Hybridization; D008297:Male; D010019:Osteomyelitis / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha