Systemic inflammatory responses in progressing periodontitis during pregnancy in a baboon model

This study tested the hypothesis that pregnant female baboons exhibit increased levels of various inflammatory mediators in serum resulting from ligature‐induced periodontitis, and that these profiles would relate to periodontal disease severity/extent in the animals. The animals were sampled at baseline (B), mid‐pregnancy (MP; two quadrants ligated) and at delivery (D; four quadrants ligated). All baboons developed increased plaque, gingival inflammation and bleeding, pocket depths and attachment loss following placement of the ligatures. By MP, both prostaglandin E2 (PGE2) and bactericidal permeability inducing factor (BPI) were greater than baseline, while increased levels of interleukin (IL)‐6 occurred in the experimental animals by the time of delivery. IL‐8, MCP‐1 and LBP all decreased from baseline through the ligation phase of the study. Stratification of the animals by baseline clinical presentation demonstrated that PGE2, LBP, IL‐8 and MCP‐1 levels were altered throughout the ligation interval, irrespective of baseline clinical values. IL‐6, IL‐8 and LBP were significantly lower in the subset of animals that demonstrated the least clinical response to ligation, indicative of progressing periodontal disease. PGE2, macrophage chemotactic protein (MCP)‐1, regulated upon activation, normal T cell expressed and secreted (RANTES) and LBP were decreased in the most diseased subset of animals at delivery. Systemic antibody responses to Fusobacterium nucleatum, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Campylobacter rectus were associated most frequently with variations in inflammatory mediator levels. These results provide a profile of systemic inflammatory mediators during ligature‐induced periodontitis in pregnant baboons. The relationship of the oral clinical parameters to systemic inflammatory responses is consistent with a contribution to adverse pregnancy outcomes in a subset of the animals.

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

[2]  G. Maso,et al.  Aetiology of preterm labour: bacterial vaginosis , 2006, BJOG : an international journal of obstetrics and gynaecology.

[3]  M. Steffen,et al.  Effects of Age and Oral Disease on Systemic Inflammatory and Immune Parameters in Nonhuman Primates , 2008, Clinical and Vaccine Immunology.

[4]  M. Timmerman,et al.  Risk factors for periodontitis. , 2006, International journal of dental hygiene.

[5]  B. Bowman,et al.  The systemic response to inflammation. , 1968, Biochemical pharmacology.

[6]  T. Sorsa,et al.  Serum microbial- and host-derived markers of periodontal diseases: a review. , 2007, Current medicinal chemistry.

[7]  S. Holt,et al.  Effects of 0.12% chlorhexidine gluconate on experimental gingivitis in non-human primates: clinical and microbiological alterations. , 2008, Oral diseases.

[8]  J. Ebersole,et al.  Etiopathogenesis of periodontitis in children and adolescents. , 2001, Periodontology 2000.

[9]  E. van Dijk,et al.  Monitoring health by values of acute phase proteins. , 2006, Acta histochemica.

[10]  G. Cook,et al.  Primer: inflammasomes and interleukin 1β in inflammatory disorders , 2008, Nature Clinical Practice Rheumatology.

[11]  M. Steffen,et al.  Periodontitis in pregnancy: clinical and serum antibody observations from a baboon model of ligature-induced disease. , 2009, Journal of periodontology.

[12]  S. Holt,et al.  Periodontal diseases: to protect or not to protect is the question? , 2001, Acta odontologica Scandinavica.

[13]  R. Romero,et al.  Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury. , 2007, Nutrition reviews.

[14]  M. Feldmann,et al.  Could toll-like receptors provide a missing link in chronic inflammation in rheumatoid arthritis? Lessons from a study on human rheumatoid tissue , 2007, Annals of the rheumatic diseases.

[15]  P. Ng,et al.  Diagnostic markers for neonatal sepsis , 2006, Current opinion in pediatrics.

[16]  J. Beck,et al.  Maternal periodontal disease in early pregnancy and risk for a small-for-gestational-age infant. , 2006, American Journal of Obstetrics and Gynecology.

[17]  Lidia Glodzik-Sobanska,et al.  Inflammation and Alzheimer's disease: Possible role of periodontal diseases , 2008, Alzheimer's & Dementia.

[18]  P Mark Bartold,et al.  Clinical relevance of the host responses of periodontitis. , 2007, Periodontology 2000.

[19]  Osamu Takeuchi,et al.  Pathogen recognition by innate receptors , 2008, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[20]  M. Tonetti,et al.  Severe periodontitis is associated with systemic inflammation and a dysmetabolic status: a case-control study. , 2007, Journal of clinical periodontology.

[21]  S. Holt,et al.  The microbiology of ligature-induced periodontitis in the cynomolgus monkey. , 1981, Journal of periodontal research.

[22]  J. Ebersole,et al.  Acute-phase reactants in infections and inflammatory diseases. , 2000, Periodontology 2000.

[23]  E. Stockfleth,et al.  Clinical investigations of Toll-like receptor agonists. , 2008, Expert opinion on investigational drugs.

[24]  G. Ekman‐Ordeberg,et al.  Non-infected preterm parturition is related to increased concentrations of IL-6, IL-8 and MCP-1 in human cervix , 2005, Reproductive biology and endocrinology : RB&E.

[25]  K. Boggess.  Pathogenicity of periodontal pathogens during pregnancy. , 2005, American journal of obstetrics and gynecology.

[26]  J. Ebersole,et al.  Humoral immune responses in gingival crevice fluid: local and systemic implications. , 2003, Periodontology 2000.

[27]  S. Holt,et al.  Immunization with Porphyromonas gingivalis cysteine protease: effects on experimental gingivitis and ligature-induced periodontitis in Macaca fascicularis. , 1998, Journal of periodontology.

[28]  S. Socransky,et al.  Microbiological goals of periodontal therapy. , 2006, Periodontology 2000.

[29]  D. Ingram,et al.  Effects of caloric restriction on inflammatory periodontal disease. , 2009, Nutrition.

[30]  R. Menon,et al.  Infection and the role of inflammation in preterm premature rupture of the membranes. , 2007, Best practice & research. Clinical obstetrics & gynaecology.

[31]  V. Fellman,et al.  Inflammation at Birth is Associated With Subnormal Development in Very Preterm Infants , 2008, Pediatric Research.

[32]  Ronald Glaser,et al.  Stress-Induced Immune Dysregulation: Implications for Wound Healing, Infectious Disease and Cancer , 2006, Journal of Neuroimmune Pharmacology.

[33]  H. Ogata,et al.  Innate immunity in inflammatory bowel disease: state of the art , 2008, Current opinion in gastroenterology.

[34]  G. Seymour,et al.  Effect of periodontal treatment on the C-reactive protein and proinflammatory cytokine levels in Japanese periodontitis patients. , 2005, Journal of periodontal research.

[35]  S. Holt,et al.  Microbiologic and immunologic characteristics of periodontal disease in Hispanic americans with type 2 diabetes. , 2008, Journal of periodontology.

[36]  J. Beck,et al.  Progressive Periodontal Disease and Risk of Very Preterm Delivery , 2006, Obstetrics and gynecology.

[37]  Purnima S. Kumar,et al.  Etiology and pathogenesis of periodontal diseases. , 2005, Dental clinics of North America.

[38]  S. Holt,et al.  Gingival crevicular fluid inflammatory mediators and bacteriology of gingivitis in nonhuman primates related to susceptibility to periodontitis. , 2000, Oral microbiology and immunology.

[39]  Thomas E Van Dyke,et al.  Risk factors for periodontitis. , 2005, Journal of the International Academy of Periodontology.

[40]  N. Terakawa,et al.  Involvement of p38 MAP kinase in lipopolysaccharide-induced production of pro- and anti-inflammatory cytokines and prostaglandin E(2) in human choriodecidua. , 2007, Journal of reproductive immunology.

[41]  S. Lye,et al.  Cytokine signaling, inflammation, innate immunity and preterm labour - a workshop report. , 2008, Placenta.

[42]  Emiel F M Wouters,et al.  Systemic inflammation in chronic obstructive pulmonary disease: the role of exacerbations. , 2007, Proceedings of the American Thoracic Society.

[43]  J. Ebersole,et al.  Systemic antibody responses to oral microorganisms in the cynomolgus monkey: development of methodology and longitudinal responses during ligature-induced disease. , 1991, Research in immunology.

[44]  R. Craig.  Interactions between chronic renal disease and periodontal disease. , 2007, Oral diseases.

[45]  G. Seymour,et al.  Interleukin-1beta, interleukin-12 and interleukin-18 levels in gingival fluid and serum of patients with gingivitis and periodontitis. , 2006, Oral microbiology and immunology.

[46]  R. Romero,et al.  The intensity of the fetal inflammatory response in intraamniotic inflammation with and without microbial invasion of the amniotic cavity. , 2007, American journal of obstetrics and gynecology.

[47]  J. Ebersole,et al.  The protective nature of host responses in periodontal diseases. , 1994, Periodontology 2000.

[48]  M. Steffen,et al.  Periodontitis in humans and non-human primates: oral-systemic linkage inducing acute phase proteins. , 2002, Annals of periodontology.

[49]  K. Boggess.  Pathophysiology of preterm birth: emerging concepts of maternal infection. , 2005, Clinics in perinatology.

[50]  D. Ingram,et al.  Differential gender effects of a reduced-calorie diet on systemic inflammatory and immune parameters in nonhuman primates. , 2008, Journal of periodontal research.

[51]  C. Coban,et al.  Host innate immune receptors and beyond: making sense of microbial infections. , 2008, Cell host & microbe.

[52]  G. Seymour,et al.  Relationship between periodontal infections and systemic disease. , 2007, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[53]  I. Clark.  How TNF was recognized as a key mechanism of disease. , 2007, Cytokine & growth factor reviews.

[54]  M. Freeman,et al.  Evidence on the Benefits and Harms of Screening and Treating Pregnant Women Who Are Asymptomatic for Bacterial Vaginosis: An Update Review for the U.S. Preventive Services Task Force , 2008, Annals of Internal Medicine.

[55]  J. Toro,et al.  Autoinflammatory diseases: clinical and genetic advances. , 2008, Archives of dermatology.

[56]  D. Sacks,et al.  Interleukin-10 and the pathogenesis of human visceral leishmaniasis. , 2007, Trends in immunology.