Alpha 2 macroglobulin of the rat, an acute phase protein, mitigates the early course of endotoxin shock.

Normal rats and rats with high levels of alpha 2 macrofetoprotein (alpha M FP), an acute phase globulin induced by pretreatment with BaSO4 i.p., were injected with sublethal doses of endotoxin. One hour survival was better in the group with high levels of alpha M FP (36%) than in controls (9%). All rats receiving purified alpha M FP i.p. survived. Recovery of mean arterial blood pressure, expressed as the surface area under the curve, was significantly better in the groups with high alpha M FP levels. Leakage of i.v. administered human albumin was the same in control and BaSO4 pretreated rats. BaSO4 induces peritonitis which could explain the albumin leakage. Experiments were repeated therefore in rats pretreated with adrenaline which also initiates the production of alpha M FP. In this group, I h survival after endotoxin administration was 100% and albumin leakage was significantly less than in rats receiving either endotoxin only or BaSO4-pretreatment. In early endotoxin shock prostaglandins, including PGE2 a potent vasodilatator, are released into the circulation. From previous data it is known that alpha M FP prevents the vasodilatation and increased vascular permeability caused by PGE2. Rats with high levels of alpha M FP had a smaller fall in diastolic blood pressure after PGE2 administration than did controls with normal alpha M FP levels. The effects of alpha M FP on the haemodynamic events in early endotoxin shock could well be due to inhibition of PGE2 activity.