Comparison of hypotensive response to aggregated IgG or to bacterial LPS in rats

Objective and Design: Rats treated with aggregated IgG (Aggr.) become ''refractory'' to the hypotensive action of a second dose of Aggr. The objective of this study was to assess the responsiveness of animals pretreated with Aggr. to bacterial LPS and vice versa. Material or Subjects: Female Wistar rats (250-300 g) were used. Each experiment was carried on at least 4 animals. Treatment: A human IgG preparation containing 30% aggregates (10-16 mg/100 g) or E. coli serotype 0111.B4 (0.005-1 mg/100 g) was administered i.v. Certain groups of animals were pretreated with 1 mg/100 g GdCl3 or with 10 mg/100 g pentoxyphylline (PTX). Methods: Arterial blood pressure was monitored in the carotis using a polyethylene cannula and an electronic tension meter. Tumor necrosis factor alpha (TNF-alpha) activity was estimated by the use of an L-929 cell cytotoxicity assay. Results: Pretreatment of rats with a sublethal dose of LPS impaired the hypotensive reaction of the animals to Aggr. Rats made ''refractory'' to Aggr. reacted to the injection of LPS with hypotension and a second phase milder than in the controls. Hypotension could not be elicited by Aggr. in rats pretreated with GdCl3. The same pretreatment had no effect on the first phase of hypotension induced by intravenous injection of LPS, whilst a mitigation of the second phase was observed. Infusion of PTX immediately prior to Aggr. administration prevented the drop of blood pressure. A sizeable level of TNF-alpha was detected only later than blood pressure had reached its minimum level following Aggr. administration. Conclusions: Hypotension induced by LPS may involve a macrophage population broader than that responsible for the vascular action of Aggr. The data presented do not support a primary role for TNF-alpha in Aggr. induced hypotension.