Reconstitution of a hyperinflammatory prostaglandin E2 response to Porphyromonas gingivalis challenge in severe combined immunodeficient mice.

BACKGROUND

The purpose of this study was to determine whether lymphocytic cells regulate the monocytic hyperinflammatory trait (MO+) in chronic periodontitis patients. Using a P. gingivalis challenge model in severe combined immunodeficient (SCID) mice, we tested the effects of adoptively transferred human peripheral blood leukocytes from gingivitis and chronic periodontitis diabetic and non-diabetic individuals on monocytic responses.

METHODS

This response was examined using the subcutaneous tissue chamber infection model. Three weeks following cell reconstitution, all SCID mice were challenged with 10(9) colony forming units of live P. gingivalis HG405. Chamber contents were collected at day 7 after bacterial challenge for prostaglandin E2 (PGE2) analysis and chamber rejection monitored up to day 30. Gingival crevicular fluid (GCF) samples were collected from all patients for PGE2 analysis. Both chamber fluid- and GCF-PGE2 levels were determined by enzyme-linked immunosorbent assays (ELISA).

RESULTS

Significantly elevated GCF-PGE2 levels were found in diabetic as well as in non-diabetic patients with moderate/advanced periodontitis compared to diabetic and non-diabetic subjects with gingivitis/mild periodontitis at P= 0.01 and P= 0.001, respectively. As reflected in chamber fluid PGE2 levels and percentage chamber rejection, lymphocytic sensitization to P. gingivalis occurred in both diabetics and non-diabetics with moderate/advanced periodontitis, but not in diabetics and non-diabetics with gingivitis/mild periodontitis.

CONCLUSIONS

These results suggest that the exaggerated monocytic inflammatory response trait (MO+) associated with moderate/advanced chronic periodontitis is due, at least in part, to lymphocytic modulation, while the directional findings for lymphocytes from diabetic subjects deserve further investigation. Our findings further demonstrate that the SCID mouse model is a useful animal model to study human immune responses to periodontal microorganisms.