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 microgram/ml of Salmonella typhimurium LPS or Prevotella intermedia LPS with or without human recombinant interferon (IFN)-gamma pretreatment. Prostaglandin E2, F2 alpha and thromboxane B2 were quantified in culture samples by gas chromatography-mass spectrometry (GC-MS) and interleukin-1 beta 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 beta 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-1 beta release in LPS-stimulated cultures from both groups. However, in susceptible patients IL-beta release was diminished after periodontal therapy in cultures pretreated with IFN-gamma. 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-gamma was followed by S. typhimurium LPS.(ABSTRACT TRUNCATED AT 250 WORDS)