Individual diversities in interferon gamma production by human peripheral blood mononuclear cells stimulated with periodontopathic bacteria

Polarization of type 1 (Th1) or type 2 (Th2) immune responses determines th e prognosis of many infectious diseases. Interferon gamma (IFN-gamma) and I L-4 are key cytokines for the development of type 1 and type 2 immune respo nses, respectively. The aim of this study was to examine individual diversi ties in the polarization of type 1 and type 2 responses against periodontop athic. bacteria. Peripheral blood mononuclear cells (PBMCs) from adult peri odontitis (AP) patients and healthy (H) subjects were stimulated with Porph yromonas gingivalis, Actinobacillus actinomycetemcomitans and Bacteroides f orsythus with or without polymyxin-B, CTLA-4 Ig and anti-IL-12 antibody. IF N-gamma, IL-4 and IL-12 in the culture supernatant were measured. IFN-gamma and IL-4 producing cells were also examined using a multiparameter flow cy tometric assay. Bone resorption rate in AP patients was calculated using Sc hei's method, and the probing pocket depth was also measured. PBMCs from AP patients and H subjects produced IFN-gamma and IL-12, whereas the producti on of IL-4 was rarely observed. Among the bacteria tested, A. actinomycetem comitans was the most potent inducer of IFN-gamma and IL-12, and the reacti on was inhibited by polymyxin-B. IFN-gamma was found to be produced by T ce lls in the PBMCs, and the production was significantly reduced by CTLA-4 Ig and anti-IL-12 neutralizing antibody. The amount of IFN-gamma produced by the PBMCs of AP patients and H subjects varied among individuals, and was s ignificantly correlated with the amount of IL-12 produced in a particular i ndividual. The production of IFN-gamma was not related with periodontal con dition which was evaluated using bone resorption and pocket depth. These re sults suggest that polarization of type 1 response against periodontopathic bacteria is dependent on the production of IL-12 by monocytes, and that IL -12 stimulates IFN-gamma production. However, individual diversities of IFN -gamma production might not be directly related to the severity of periodon titis.