PROSTAGLANDIN E(2) REGULATES GINGIVAL MONONUCLEAR CELL IMMUNOGLOBULIN PRODUCTION

HISTOLOGICAL STUDIES HAVE REVEALED elevated levels of T and B lymphocytes in inflamed gingival tissue. Functional analysis of these B cells has determined that they are spontaneously secreting large amounts of immunoglobulin. Several components of bacterial plaque which accumulate during the onset of periodontal disease induce polyclonal B cell activation, and are most likely responsible for the ''hyperactive'' state of these gingival B lymphocytes. In addition to this exaggerated humoral response, increased levels of inflammatory mediators, such as prostaglanidin (PG) E(2), have been implicated in the pathogenesis of disease. Therefore, the purpose of this study was to determine if PGE(2) could regulate immunoglobulin production within inflamed gingival tissue. Specimens were harvested during routine surgery of patients with chronic adult periodontitis. Utilizing an ELISA, elevated levels of IgG were detected in the supernatant of cultured gingival mononuclear cells. Inclusion of indomethacin, which inhibits arachidonic acid metabolites such as PGE(2), caused a decrease in IgG levels. PGE(2) exerted a biphasic effect upon IgG production, with high doses diminishing and low doses increasing IgG levels. From a clinical perspective, these results suggest that elevated levels of PGE(2) associated with inflammation will attenuate an IgG response and, as PGE(2) production wanes, the local humoral response will rebound. Interestingly, the combination of low dose PGE(2) and IL-4 induced a synergistic rise in IgG production. These findings support the theory that local PGE(1) levels can regulate immunoglobulin production and potentiate cytokine induced class switching within gingival tissue.