Effect of Macrophage Inhibition in Carrageenan- and d-Galactosamine-Induced Sensitivity to Low-Dose Endotoxin

摘要

These studies indicate that macrophage function is necessary in vivo to permit the lethal effects of LPS in carrageenan- and D-galactosamine-sensitized mice. Silica particles, cytotoxic for macrophages, prevented the lethal effects of low-dose LPS in both carrageenan and D-galactosamine models. Similarly, polyclonal antibodies against TNF given prior to D-galactosamine can prevent the subsequent lethal effects of low-dose LPS (data to be published elsewhere). Clearly, inhibition of macrophage function or neutralization of TNF are methods for preventing the effects of endotoxemia in murine models. An attempt to inhibit TNF production and/or release by macrophages was made with trypan blue, which has been described in the literature to block TNF production (Satomi et al., 1981). However, trypan blue failed to alter the lethal effects of low-dose LPS in the experimental models. In vitro and in vivo studies are under way to determine the specific effects of trypan blue and other inhibitors of macrophage accessory cell functions on the production and release of TNF. These studies may possibly lead to the identification of inhibitors of macrophage functions, particularly those specific for the production of TNF. Inhibitors of macrophage TNF production may have therapeutic potential in septic shock. Keywords: Tumor necrosis factor, Sepsis. Reprints. (aw)