Peritoneal macrophages from endotoxin-tolerant mice produce an inhibitor of tumor necrosis factor α synthesis and protect against endotoxin shock

Abstract

In the present study it was found that development of early endotoxin-tolerance is associated with the capacity of mouse peritoneal macrophages (MPM) to produce an activity interfering with the synthesis of tumor necrosis factor α. Peritoneal macrophages from LPS-tolerant mice (tMPM), treated with LPS in vitro produced less TNFα, IL-10 and TGFβ than LPS-treated macrophages from normal mice (nMPM). The supernatants of LPS-activated tMPM contained activities which suppressed formation of TNF in nMPM and RAW 264.7 cells as determined by bioassay, ELISA and PCR. Supernatants of nMPM and unstimulated tMPM were devoid of the inhibitory activity. The inhibitor did not interfere with the bioactivity of TNFα in WEHI cells. It also suppressed PMA/IFN-γ induced TNF synthesis in macrophage cultures. The transfer of macrophages isolated from endotoxin-tolerant mice into normal mice protected against endotoxin shock, whereas macrophages from normal mice increased susceptibility to endotoxin.