Longitudinal evaluation of peripheral blood monocyte secretory function in periodontitis-resistant and periodontitis-susceptible patients

The purpose of this investigation was to evaluate lipopolysaccharide (LPS)-stimulated monocyte secretory responses longitudinally in patients with generalized severe chronic adult periodontitis (periodontitis-susceptible) and controls with gingivitis (periodontitis-resistant). In addition, the expression of constitutive (Leu-M3) and LPS-inducible (Mo3e) antigens on monocytes isolated from these two groups was examined. Monocyte secretory function was assessed longitudinally; the effect of periodontal therapy in the susceptible patients was examined by comparing monocyte function before and after their treatment. Peripheral blood monocytes were isolated by counterflow centrifugal elutriation and treated with control medium or media containing 1 μg/ml of Salmonella typhimurium LPS orPrevotella intermedia LPS with or without human recombinant interferon (IFN)-γ pretreatment. Prostaglandin E₂, F_2α and thromboxane B₂ were quantified in culture samples by gas chromatography-mass spectrometry (GC-MS) and interleukin-1β was quantified by enzyme-linked immunosorbent assay. Leu-M3 and Mo3e antigen expression was assessed by FACScan. Three major findings were made. First, LPS-stimulated IL-1 β release by monocytes from susceptible patients was depressed relative to that in resistant patients at the initial donation. After periodontal therapy, there was virtually identical IL-1β release in LPS-stimulated cultures from both groups. However, in susceptible patients IL-β release was diminished after periodontal therapy in cultures pretreated with IFN-γ. Second, there was a significant drift in monocyte secretion of prostaglandin E₂ in samples from the resistant patients between the first two donations and the third donation. PGE₂ release did not differ between groups at the initial donation, although there was a depression in PGE₂ release in the susceptible group at the final donation when IFN-γ was followed by S. typhimurium LPS. Finally, P. intermedia LPS relative to S. typhimurium LPS selectively potentiated PGE₂ release in the samples from the susceptible group after IFN-γ pretreatment. This effect was observed for all donations. These data suggest that IFN-γ priming results in monocyte differentiation processes that are not the same in both groups. Therefore, the local determinants of macrophage activation require further evaluation. These differences between resistant and susceptible patients may be most evident in inflamed gingival tissue where macrophages have been exposed to the inflammatory milieu.