Increased interleukin-1 and modulation of interleukin-2 production by murine macrophages and lymphocytes treated with LF 1695.

ABSTRACT

Previous results have demonstrated that lectin-induced T cell proliferation was potentiated or suppressed by LF 1695, a synthetic immunomodulator, depending on the dose used. Therefore the activity of this compound was investigated on murine IL-1 and IL-2 production. Adherent peritoneal cells, incubated with LF 1695, could secrete high levels of IL-1 with only a slight elevation in intracellular IL-1. This effect apparent at 5 and 10 micrograms/ml was linked to a transient state of activation. At low doses, LF 1695 increased IL-2 production by Con A-stimulated spleen cells. A decrease was found at higher doses only when cells were preincubated 20 h with the compound. In murine macrophages stimulated either by A 23187 or LPS PGE2 synthesis was inhibited by LF 1695 even at low doses. However, supernatant LTB4 level was increased in LF 1695-treated culture with a time-dependent effect. Therefore modulation of lectin-induced T cell proliferation by LF 1695 may be IL-2 production-mediated. Inhibition of the cyclooxygenase and stimulation of the lipoxygenase pathway of arachidonic acid metabolism may be responsible for this pattern of activity.