LOCAL EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA IN AN EXPERIMENTAL-MODEL OF ACUTE OSTEOMYELITIS IN RATS

The inflammatory response associated with Staphylococcus aureus osteom yelitis results in extensive bone damage characterized by apparent inc reases in bone resorption and formation, These results suggest an incr eased 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 unc lear, 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 h igh (approximately 6 log(10) CFU/g of bone over 63 days) and bone weig hts increased. TNF activity was undetectable in uninfected bone (< 0.0 1 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 un infected bone, osteomyelitis was associated with up to 37-fold increas es in expression of both the 1.6- and 2.4-kb transcripts, Both TNF act ivity and mRNA transcript levels remained elevated throughout the cour se of infection, TNF-alpha mRNA detected by in situ hybridization was present in osteoblasts as well as in populations of marrow cells and/o r inflammatory infiltrate cells. Histopathology of infected bone indic ated extensive bone resorption and adjacent areas of formation that we re 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 osteomyel itis.