Endotoxin-lnduced Release of Interleukin 6 and Interleukin 1β in Human Blood Is Independent of Tumor Necrosis Factor Alpha

It has been suggested that tumor necrosis factor alpha (TNFα) acts not only by direct toxicity, but also as a proximal mediator which is able to induce the production of other cytokines, especially interleukin 6 (IL-6) and interleukin 1β (IL-1β). In order to test the dependence of the release of these two cytokines from leukocytes upon induction by TNFα, we stimulated whole blood in vitro with TNFα and compared the cytokine levels with those induced by endotoxin. The cytokine release was also determined after stimulation by endotoxin with added TNFα and by endotoxin with monoclonal antibodies against TNFα (anti-TNFα) added in order to reduce TNFα. Unstimulated blood samples were used as controls. The plasma levels of both IL-6 and IL-1β were significantly higher after stimulation with endotoxin than after stimulation with TNFα. TNFα did not induce cytokine levels significantly higher than controls. The cytokine levels were the same whether or not anti-TNFα was included together with the endotoxm. Plasma from samples with added anti-TNFα had no detectable TNFα. Our results indicate that the leukocyte-derived production of IL-6 and IL-1β in whole blood is stimulated directly by endotoxin and is not mediated by TNFα.