Soluble antagonists to interleukin-1 (IL-1) and tumor necrosis factor (TNF) inhibits loss of tissue attachment in experimental periodontitis.
OBJECTIVE
Periodontal disease is a significant cause of tooth loss among adults and is characterized by the alteration and permanent destruction of the deeper periodontal tissues. Although the presence of pathologic microbes is required to trigger this process, the amplification and progression of the diseased state is believed to rely heavily on the production of host mediators in response to bacteria or their metabolic products. The inflammatory response is effective in preventing large-scale colonization of the gingival tissues by bacteria that lie in close proximity to the tooth surface or within the gingival sulcus. It has been postulated that the host-response in some individuals may lead to an over-reaction to invading oral pathogens resulting in the destruction of periodontal tissues.


METHODS
Several host-derived mediators are believed to contribute to this response. Two agents considered to be essential in periodontal destruction are interleukin-1 (IL-1) and tumor necrosis factor (TNF). We investigated the role of IL-1 and TNF in the loss of connective tissue attachment in a Macaca fascicularis primate model of experimental periodontitis. Silk ligatures impregnated with the periodontal pathogen, Porphyromonas gingivalis were wrapped around the posterior teeth and the activity of IL-1 and TNF were inhibited by soluble receptors to these proinflammatory cytokines via local injection into interdental papillae.


RESULTS
Histomorphometric analysis indicates that IL-1 and TNF antagonists significantly reduced the loss of connective tissue attachment by approximately 51% and the loss of alveolar bone height by almost 91%, both of which were statistically significant.


CONCLUSIONS
This investigation demonstrates that the loss of connective tissue attachment and progression of periodontal disease can be retarded by antagonists to specific host mediators such as IL-1 and TNF and may provide a potential treatment modality to combat the disease process.
Delima
A J
AJ
Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, MA, USA.
Oates
T
T
Assuma
R
R
Schwartz
Z
Z
Cochran
D
D
Amar
S
S
Graves
D T
DT
D016301:Alveolar Bone Loss / Q000382:microbiology / Q000517:prevention & control; D000818:Animals; D016866:Bacteroidaceae Infections; D003238:Connective Tissue / Q000187:drug effects / Q000382:microbiology; D004195:Disease Models, Animal; D018450:Disease Progression; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008252:Macaca fascicularis; D017622:Periodontal Attachment Loss / Q000382:microbiology / Q000517:prevention & control*; D010518:Periodontitis / Q000382:microbiology / Q000517:prevention & control*; D016966:Porphyromonas gingivalis / Q000502:physiology; D012995:Solubility; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018836:Inflammation Mediators; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha