Muramyl dipeptide induces production of hemopoietic growth factors in vivo by a mechanism independent of tumor necrosis factor.

Abstract

Monocyte products including TNF and IL-1 can stimulate hemopoietic growth factor production in vitro and in vivo. Endotoxin-resistant C3H/HeJ mice have a cellular defect in the regulation of TNF production and provide a model in which to examine the relative importance of TNF and IL-1. To assess the relative role of TNF and IL-1, we injected the synthetic bacterial cell wall derivative muramyl dipeptide (MDP) or LPS into C3H/HeJ mice. Both MDP and LPS stimulated hemopoietic growth factor production in a dose-dependent manner. Northern blot analysis of splenic and lung mRNA revealed that MDP treatment induced granulocyte-macrophage CSF and macrophage-CSF transcripts, whereas LPS treatment induced macrophage-CSF transcripts. Messenger RNA for granulocyte-CSF, IL-3, IL-4, and IL-5 was not detected in control or treated mice. MDP treatment induced IL-1 mRNA but not TNF mRNA, and TNF bioactivity was not detected in the serum of MDP-treated mice. In contrast, LPS treatment induced TNF production. These results identify the hemopoietic growth factors induced by MDP and LPS in vivo, and suggest that MDP stimulates growth factor production by a mechanism independent of TNF.