- 1We studied endotoxin (lipopolysaccharide, LPS)-induced platelet-activating factor (PAF) production in various visceral organs, and the effect of PAF antagonists or splenectomy on LPS-induced changes.
- 2PAF production in response to LPS was highest in the spleen, followed by ileum, heart, lung and kidneys. None was found in the liver. The splenic response was rapid, reaching 10 times the basal level at 30 min. The increased PAF content in each organ was unrelated to the enzyme activity of either macrophages or neutrophils.
- 3LPS-induced hypotension and haemoconcentration were largely prevented by PAF antagonists and splenectomy.
- 4Plasma volume fell, and plasma atrial natriuretic peptide (ANP) rose, after LPS administration. Splenectomy or pretreatment with PAF antagonists almost completely prevented these LPS-induced changes at 30 min, but only partially reversed them at 90 min.
- 5These results suggest that during endotoxaemia: (a) the spleen is the site of the highest endogenous PAF production; (b) the initial release of ANP is dependent on the production of endogenous PAF, and a PAF-ANP interaction mediates the early plasma volume reduction; (c) plasma volume reduction as well as ANP release depend on the spleen; (d) PAF mediated the hypotensive response and its action in the spleen; and (e) sequestered neutrophils are probably not the main source of PAF in the spleen.