A type 2 response in lipopolysaccharide (LPS)-stimulated whole blood cell cultures from periodontitis patients

Abstract

It 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 E2 (PGE2), IL-1beta, IL-6, IL-8, IL-10, IL-12p40, IL-12p70 and tumour necrosis factor-alpha (TNF-alpha) was measured. The levels of PGE2 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-1beta 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-alpha production. It is known from the literature that LPS-stimulated 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 PGE2 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 PGE2 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.

Fig. 1

LPS-induced mediator production in 19 periodontitis patients and 19 controls. For the measurements of IL-1β, IL-6, IL-8, IL-10, IL-12p40, tumour necrosis factor-alpha (TNF-α) and prostaglandin E₂ (PGE₂) the whole blood cell cultures were stimulated with 1 ng/ml LPS from Escherichia coli for 18 h, whereas the cultures for IL-12p70 were stimulated with 100 ng/ml LPS from E. coli for 18 h. Data are means ± s.e.m. and are expressed as cytokine or PGE₂ production per 10⁶ monocytes. The individual data per subject were the mean of two different cultures. *P < 0·05; **P < 0·01 as determined by analysis of covariance, with age, race and number of monocytes as co-variants. □, Controls; ▪, patients.