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Clinical and Vaccine Immunology, July 2008, p. 1067-1075, Vol. 15, No. 7
1071-412X/08/$08.00+0     doi:10.1128/CVI.00258-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Effects of Age and Oral Disease on Systemic Inflammatory and Immune Parameters in Nonhuman Primates

Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, Kentucky,¹ Caribbean Primate Research Center, University of Puerto Rico, Sabana Seca, Puerto Rico²

Received 26 June 2007/ Returned for modification 5 November 2007/ Accepted 18 April 2008

This report evaluated systemic inflammatory and immune biomarkers in a cohort of Macaca mulatta (rhesus monkeys) maintained as a large family social unit, including an age range from <1 year to >24 years. We hypothesized that the systemic host responses would be affected by the age, gender, and clinical oral presentation of the population, each contributing to inflammatory and immune responses that would reflect chronic oral infections. The results demonstrated that the prevalence and severity of periodontitis, including missing teeth, increased significantly with age. Generally, minimal differences in clinical parameters were noted between the genders. Systemic inflammatory mediators, including acute-phase reactants, prostaglandin E₂ (PGE₂), cytokines/chemokines, and selected matrix metalloproteinases (MMP), demonstrated significant differences among the various age groups of animals. Levels of many of these were increased with age, although PGE₂, RANTES, bactericidal permeability-inducing factor (BPI), MMP-1, and MMP-9 levels were significantly increased in the young group (1 to 3 years old) relative to those for the older animals. We observed that in the adult and aged animals, levels of the systemic inflammatory mediators related to gingival inflammation and periodontal tissue destruction were significantly elevated. Serum antibody levels in response to a battery of periodontal pathogens were generally lower in the young animals, <50% of those in the adults, and were significantly related to aging in the cohort. The levels of antibodies, particularly those to Porphorymonas gingivalis, Fusobacterium nucleatum, and Tannerella forsythia, were most significantly elevated in animals with periodontal disease, irrespective of the age of the animal. These results provide a broad description of oral health and host responses in a large cohort of nonhuman primates from very young animals to the aged of this species. The findings afford a base of data with which to examine the ontogeny of host responses at mucosal sites, such as the gingival tissues.

Published ahead of print on 30 April 2008.