Hyperlipidemia causes changes in inflammatory responses to periodontal pathogen challenge: Implications in acute and chronic infections

Objective: In this study, the effect of hyperlipidemia on immune responses to periodontal bacterial infections was investigated. Methods: Sixty male New Zealand white rabbits were equally assigned to normal diet (ND) and high-fat diet (HFD) for 6 weeks. Every six rabbits with ND or HFD were orally inoculated with live Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis three times a week for 8 weeks. Also every six rabbits with ND or HFD rabbits were injected intravenously with A. actinomycetemcomitans and P. gingivalis LPS. Periodontal disease severity was quantified by macroscopic and radiographical evaluation. Serum cytokines were examined by enzyme-linked immunosorbent assay. In vitro, peripheral mononuclear cells were collected and stimulated with LPS. Quantitative real-time polymerase chain reaction was used to determine the changes in gene expression of macrophages. Results: In the early stages of infection, HFD rabbits were exposed to oral infection and systemic infection developed a weak inflammatory response to the reduced cytokine expression compared with ND rabbits. However, HFD rabbits exhibited higher inflammatory cytokine expression during long-term infections. Moreover, the pronounced changes in inflammatory cytokine expression elicited a significantly increase in bone loss in HFD rabbits with oral infection. Peripheral macrophages harvested from HFD rabbits and exposed to LPS exhibited reduced levels of pro-inflammatory cytokines compared with those from ND rabbits in vitro. Conclusion: These data indicated that hyperlipidemia interfered with immune responses differently. The mechanism is possibly associated with immune paralysis in the acute phase and accumulation of inflammatory mediators in the chronic period. (C) 2014 Elsevier Ltd. All rights reserved.