Gingival fibroblast cytokine profiles in Actinobacillus actinomycetemcomitans-associated periodontitis.

Abstract

Within the in vivo environment human gingival fibroblasts (HGF) may be challenged with bacteria or bacterial products. This interaction may result in the release of cytokines which are directly or indirectly involved in connective tissue and bone catabolism, such as interleukin (IL)-1 beta, IL-6, and IL-8. Our investigation has tested the hypothesis that HGF from Actinobacillus actinomycetemcomitans (Aa)-infected patients with rapidly destructive forms of periodontitis, such as localized juvenile periodontitis (LJP), respond to Aa challenge with an exaggerated secretion of IL-1 beta, IL-6, and IL-8. We have compared the in vitro profiles of these cytokines by Aa-challenged HGF obtained from 2 healthy subjects, 2 Aa-infected, slowly progressing adult periodontitis (AP) patients and 2 LJP patients. HGF were challenged throughout a 48-hour period with formalinized whole bacterial cells, and culture supernatants were analyzed for cytokine content using RIA. No differences were noted in the IL-1 beta secretion levels among the different HGF cultures. Although basal (unchallenged) IL-6 and IL-8 production was similar in all HGF cultures, HGF from the two LJP patients responded to Aa challenge with a more rapid IL-6 and a more pronounced IL-8 secretion than healthy or AP HGF. We also tested the ability of human serum antibodies against Aa to moderate the Aa-elicited HGF cytokine secretion by adding human serum, with normal or elevated antibody content. Both sera appeared to have an upregulating effect on IL-6 and IL-8 secretion. Depletion of 95% of the anti-Aa antibody from serum by absorption did not affect its activity. Based on the response of HGF from two LJP patients, we propose that Aa-induced pathology in LJP may be modulated by stimulation of rapid and/or exaggerated secretion of cytokines with potential catabolic effects, although studies with a larger group of LJP patients are needed to further test this hypothesis. Furthermore, serum antibodies against this microorganism do not appear to have a neutralizing effect in cytokine-eliciting HGF-Aa interactions.