LIPOPOLYSACCHARIDE-INDUCED PRODUCTION OF TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-1 IS DIFFERENTIALLY REGULATED AT THE RECEPTOR LEVEL - THE ROLE OF CD14-DEPENDENT AND CD14-INDEPENDENT PATHWAYS

Cytokine production induced via CD14-dependent and CD14-independent pa thways was investigated in mouse peritoneal macrophages incubated with lipopolysaccharide (LPS) or lipid A. Different LPS receptors appear t o be responsible for production of tumour necrosis factor-alpha (TNF-a lpha) and interleukin-1 alpha (IL-1 alpha) and IL-1 beta. TNF-alpha pr oduction is essentially CD14 dependent, both in the presence or absenc e of plasma. In the presence of plasma, endotoxin-induced IL-1 product ion is mediated by CD14-dependent mechanisms, while in its absence bot h CD14-dependent and CD14-independent pathways are involved. Lipid A s timulates cytokine synthesis through both CD14-dependent and CD14-inde pendent mechanisms, but its action is weaker than that of LPS, indicat ing that the polysaccharide moiety may be necessary for proper stimula tion of mouse macrophages by endotoxin.