SUMMARYIt is acknowledged that periodontitis results from the interaction of the host immune response with bacteria accumulating on the tooth surfaces. Although bacteria are essential, they are insufficient to cause the disease. Despite this knowledge it remains unclear why certain individuals are more susceptible to periodontitis than others. Therefore the present study investigated whether differences exist in the actual immune response between periodontitis patients and controls after stimulation of peripheral blood cells. Whole blood cell cultures (WBCC) were stimulated with LPS from Escherichia coli during 18 h and the release of prostaglandin E 2 (PGE 2 ), IL-1b, IL-6, IL-8, IL-10, IL-12p40, IL-12p70 and tumour necrosis factor-alpha (TNF-a) was measured. The levels of PGE 2 were two-fold higher in the WBCC from periodontitis patients than from controls. In contrast, the levels of IL-12p70 in WBCC from patients were two-fold lower. Furthermore, WBCC from patients secreted lower levels of IL-1b and higher levels of IL-8 when compared with WBCC from controls. No differences were observed with respect to IL-6, IL-10, IL-12p40 and TNF-a production. It is known from the literature that LPSstimulated WBCC reflect specifically the behaviour of the monocytes and that monocytes are peripheral precursors of antigen-presenting cells (APC). Therefore it is concluded that the monocytes in the present WBCC from periodontitis patients are responsible for the higher levels of PGE 2 and lower levels of IL-12p70. Since it is has been shown that APC-derived IL-12p70 induces type (Th1) cells that promote cellular immunity, while APC-derived PGE 2 induces type 2-helper (Th2) cells that promote humoral immunity, it is postulated that APC from periodontitis patients may have a bias in directing Th2 responses and thereby promoting the humoral immunity in periodontitis.

SUMMARYBacteria colonizing tooth surfaces are essential in the induction of an inflammatory response in the periodontal tissues, but do not cause periodontitis in everyone, implicating differences in the host immune response. These possible differences were studied using lipopolysaccharide (LPS)-stimulated whole blood cell cultures (WBCC), which revealed a down regulation of monocyte derived interleukin-12 (IL12p70) in untreated periodontitis patients and an up regulation after therapy. IL-12p70 is a crucial factor in the differentiation of Th1 cell responses. Since CC chemokines are able to influence the T cell differentiation via cytokine secretion in antigen-presenting cells, the production of CC chemokines in periodontitis was evaluated. Therefore WBCC were stimulated with LPS from Escherichia coli for 18 h and the levels of IL-12p70 and CC chemokines were measured in the supernatants by ELISA. Untreated periodontitis patients released 2 fold more RANTES (regulated on activation normal T cell expressed and secreted) ( P = 0·01) and lower levels of IL-12p70 in comparison to controls ( P < 0·05). A trend towards higher levels of macrophage chemoattractant protein-1 (MCP-1) ( P = 0·07) was also seen in untreated periodontitis patients; while similar levels of monocyte derived chemokine (MDC) and macrophage inflammatory proteins-1 a and -1 b (MIP-1 a and -1 b ) were found. After periodontal therapy no changes were seen with regard to MDC, MIP-1 a , MIP-1 b and RANTES, whereas the MCP-1 levels decreased ( P < 0·05) and the IL-12p70 levels strongly increased ( P < 0·01). The data showed a consistent inverse correlation between the levels of MCP-1 and IL-12p70, and their proportional changes after therapy correlated with the clinical inflammatory response after therapy. This indicates that the disease state regulates the release of IL-12p70 and MCP-1 in E. coli LPS-stimulated WBCC. In contrast, the persistent augmented levels of RANTES after therapy are suggestive for an intrinsic behaviour.

After periodontal therapy, the functional phenotype of the peripheral blood monocytes from patients was reconstituted, resembling that of subjects without periodontitis.

Periodontitis results from the interaction of bacteria on the tooth surfaces and the host immune response. Although periodontal pathogens are essential for the initiation and progression of the disease, the tissue damage in periodontitis is primarily mediated by the host immune response. Differences in the susceptibility to the disease and in the clinal outcome of the therapy seem to be less dependent on genetics but more on lifestyle factors, like smoking, overweight, stress and nutrition. It has been shown that these lifestyle factors may modulate the immune response and therefore influence the initiation and progression of the disease. To study the host immune response, whole blood cell cultures (WBCC) stimulated with lipopolysaccharide (LPS) have been widely used and they specifically reflect the behaviour of monocytes. It has been shown that peripheral blood monocytes in LPS-stimulated WBCC from non-smoking periodontitis patients display a T-helper 2 (Th2)-promoting phenotype in comparison with controls. After periodontal therapy, this phenotype reversed and was comparable with controls. However, in smoking but treated patients, the Th2-promoting phenotype of monocytes still remained. Therefore, the aberrant phenotype of monocytes in the peripheral blood from periodontitis patients is likely to be a systemic response to exogenous and endogenous danger molecules released or induced by the periodontal infection or by smoking. It can be concluded that periodontal therapy in non-smoking periodontitis patients has beneficial health effects and that smoking cessation should be an integral part of the therapy as well for general health reasons as for the clinical outcome.