The interrelation between TNF, IL-6, and PAF secretion induced by LPS in an in vivo and in vitro murine model.

The interrelation between TNF, IL-6, and PAF secretion in an in vivo and in vitro murine model was studied. Mice were injected with LPS, giving rise to considerable TNF and IL-6 serum levels. To determine the influence of TNF production on the IL-6 secretion, one group of mice was treated with an anti-TNF mAb before LPS administration. The LPS-induced IL-6 secretion was reduced to 48% in the anti-TNF-pretreated group. Parallel to the in vivo experiments, cultures of murine peritoneal macrophages were stimulated with LPS. IL-6 secretion was diminished for 25% in presence of anti-TNF mAb. Further, the role of PAF released in response to a challenge with LPS in the regulation of TNF and IL-6 production was investigated. TNF secretion was strongly reduced when cultures of peritoneal macrophages were stimulated with LPS in the presence of a PAF antagonist, whereas IL-6 secretion was not altered by the PAF antagonist. However, pretreatment of mice with a PAF antagonist did not influence serum TNF, nor serum IL-6 levels induced by LPS injection. These data show that TNF was an intermediate in the induction of IL-6 production in vivo and in vitro. PAF played a central role in the TNF release in the in vitro experiments. This could, however, not be established in vivo. LPS-induced PAF secretion was not involved in the regulation of IL-6 secretion.