Stimulation of lymphocyte migration by endotoxin, tumor necrosis factor, and interferon

Since several studies have demonstrated that lipopolysaccharide (LPS), tumor necrosis factor (TNF), and interleukin-1 (IL-1) enhanced lymphocyte binding to endothelial cells in vitro, we examined the effects of these agents on lymphocyte migration in vivo. Small peritoneal exudate lymphocytes (sPEL), which preferentially migrate into inflammatory sites, were radiolabeled with ¹¹¹In and injected iv into rats. The id injection of LPS was a strong stimulus for the migration of these cells into the skin. TNFα was also a good stimulator of lymphocyte migration, while TNFβ and IL-1α were weak or nearly inactive. Kinetic analysis demonstrated that migration to TNF was rapid, with a peak at 6 hr, followed by a steady decline, while migration to LPS was sustained for 24 hr. TNFα, TNFβ, and IL-1α, when combined with interferon-γ (IFN-γ) or IFN- α β produced striking synergistic increases in lymphocyte migration. Combinations of the TNFs and IL-1 had less than additive effects, as did combinations of the IFNs. Qualitatively similar migration responses were found when spleen T cells instead of sPEL were studied.