Inflammation and tissue loss caused by periodontal pathogens is reduced by interleukin-1 antagonists.

Periodontal disease is a significant cause of tooth loss among adults. It is initiated by pathogenic bacteria, which trigger an inflammatory response that is effective in preventing significant microbial colonization of the gingival tissues. In some individuals, the reaction to bacteria may lead to an excessive host response, resulting in periodontal tissue destruction. Recent developments suggest that interleukin (IL)-1 genetic polymorphisms may identify certain individuals who have a predisposed susceptibility to periodontal breakdown and that elevated levels of IL-1 are found in individuals with periodontal disease. However, there is no direct evidence that IL-1 per se is responsible for the critical events that occur in periodontitis. We investigated the role of IL-1 in periodontal disease in a Macaca fascicularis primate model, using human soluble IL-1 receptor type I as a specific inhibitor. The results indicate that inhibition of IL-1 alone significantly reduces inflammation, connective tissue attachment loss, and bone resorption that are induced by periodontal pathogens.

[1]  D. Graves,et al.  Tumor Necrosis Factor Modulates Fibroblast Apoptosis, PMN Recruitment, and Osteoclast Formation in Response to P. gingivalis Infection , 2001, Journal of dental research.

[2]  R. Poulton,et al.  IL-1 Genotype and Adult Periodontitis among Young New Zealanders , 2001, Journal of dental research.

[3]  J. Vandenbroucke,et al.  Polymorphisms of the Interleukin-1 Gene Family, Oral Microbial Pathogens, and Smoking in Adult Periodontitis , 2001, Journal of dental research.

[4]  J. Dayer,et al.  Anti–interleukin-1 therapy in rheumatic diseases , 2001, Current opinion in rheumatology.

[5]  D. Graves,et al.  Soluble antagonists to interleukin-1 (IL-1) and tumor necrosis factor (TNF) inhibits loss of tissue attachment in experimental periodontitis. , 2001, Journal of clinical periodontology.

[6]  P. Papapanou,et al.  Cytokine Responses of Oral Epithelial Cells to Porphyromonas gingivalis Infection , 2000, Journal of dental research.

[7]  S. Takashiba,et al.  Induction of Intracellular Interleukin-1 β Signals via Type II Interleukin-1 Receptor in Human Gingival Fibroblasts , 2000, Journal of dental research.

[8]  T. Martin,et al.  Therapeutic approaches to bone diseases. , 2000, Science.

[9]  D. Graves,et al.  Interleukin-1 Receptor Signaling Rather than That of Tumor Necrosis Factor Is Critical in Protecting the Host from the Severe Consequences of a Polymicrobe Anaerobic Infection , 2000, Infection and Immunity.

[10]  N. Rothwell,et al.  Potential mechanisms of interleukin-1 involvement in cerebral ischaemia , 1999, Journal of Neuroimmunology.

[11]  D. Graves,et al.  Periodontal pathogens stimulate CC-chemokine production by mononuclear and bone-derived cells. , 1999, Journal of periodontology.

[12]  H. M. Lee,et al.  A Chemically Modified Nonantimicrobial Tetracycline (CMT‐8) Inhibits Gingival Matrix Metalloproteinases, Periodontal Breakdown, and Extra‐Oral Bone Loss in Ovariectomized Rats , 1999, Annals of the New York Academy of Sciences.

[13]  R. Atkins,et al.  IL-1 up-regulates osteopontin expression in experimental crescentic glomerulonephritis in the rat. , 1999, The American journal of pathology.

[14]  D. Graves,et al.  Interleukin-1 and tumor necrosis factor antagonists inhibit the progression of inflammatory cell infiltration toward alveolar bone in experimental periodontitis. , 1998, Journal of periodontology.

[15]  K. McIntyre,et al.  IL-1 receptor accessory protein is an essential component of the IL-1 receptor. , 1998, Journal of immunology.

[16]  G. Seymour,et al.  Cytokine Profiles of Cells Extracted from Humans with Periodontal Diseases , 1998, Journal of dental research.

[17]  D. Graves,et al.  IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. , 1998, Journal of immunology.

[18]  D. Dudley Pre-term labor: an intra-uterine inflammatory response syndrome? , 1997, Journal of reproductive immunology.

[19]  C. Dinarello,et al.  Biologic basis for interleukin-1 in disease. , 1996, Blood.

[20]  T. Takishima,et al.  Potential role of interleukin-1 in allergen-induced late asthmatic reactions in guinea pigs: suppressive effect of interleukin-1 receptor antagonist on late asthmatic reaction. , 1995, The Journal of allergy and clinical immunology.

[21]  A. Mantovani,et al.  The type II 'decoy' receptor: a novel regulatory pathway for interleukin 1. , 1994, Immunology today.

[22]  M. Peters,et al.  Human cutaneous allergic late-phase response is inhibited by soluble IL-1 receptor. , 1994, Journal of immunology.

[23]  S. Schou,et al.  Non-human primates used in studies of periodontal disease pathogenesis: a review of the literature. , 1993, Journal of periodontology.

[24]  H. Birkedal‐Hansen Role of Matrix Metalloproteinases in Human Periodontal Diseases. , 1993, Journal of periodontology.

[25]  K. Huebner,et al.  A novel IL‐1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. , 1991, The EMBO journal.

[26]  H. Löe,et al.  Periodontal diseases in the U.S. in 1981: prevalence, severity, extent, and role in tooth mortality. , 1989, Journal of periodontology.

[27]  Y. Ohmori,et al.  Functional role of interleukin 1 in periodontal disease: induction of interleukin 1 production by Bacteroides gingivalis lipopolysaccharide in peritoneal macrophages from C3H/HeN and C3H/HeJ mice , 1985, Infection and immunity.

[28]  R. Williams,et al.  Flurbiprofen: a potent inhibitor of alveolar bone resorption in beagles. , 1985, Science.

[29]  H. Miller,et al.  Pathophysiological role of cytokines in congestive heart failure. , 2001, Annual review of medicine.

[30]  G. Duff,et al.  The interleukin-1 genotype as a severity factor in adult periodontal disease. , 1997, Journal of clinical periodontology.

[31]  A. Ferrante Activation of neutrophils by interleukins-1 and -2 and tumor necrosis factors. , 1992, Immunology series.

[32]  P. Stashenko,et al.  Localization of Interleukin‐lβ in Human Periodontal Tissue , 1991 .

[33]  H. McClure,et al.  Changes in cyclooxygenase metabolites in experimental periodontitis in Macaca mulatta. , 1989, Journal of periodontal research.

[34]  S. Holt,et al.  Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis. , 1988, Science.