On the Nature of Tolerance of Endotoxin. ∗

Abstract

Tolerance of endotoxin has been found to be related to the pinocytic and phagocytic capacity of the reticulo-endothelial system (1–4). Recently the plasma of the tolerant animal has been found to contain a transferable factor that suppresses pyrogenicity and increases the rate of phagocytosis in the recipient (5–7). Such data, though doubtless of considerable significance, do not sufficiently explain what it is that constitutes increased tolerance.

We have reported the presence in normal spleen of a protein with an esterase-like behavior (8) which is capable of rapidly degrading endotoxin(9), as indicated by tests: a, for toxicity of endotoxin for the 10-day-old chick embryo, and for the pertussis-treated mouse (10), and b, for the capacity of endotoxin to fix complement on exposure to specific antibody.† That this protein can alter the endotoxin molecule was also demonstrated by its ability to block 2 phage receptor sites on the endotoxin molecule,‡ and by production of multiple precipitation bands, instead of a single one, on Ouchterlony plates. The validity of these tests for assessing the presence or absence of potency in this protein fraction of spleen was affirmed by the finding that the results by more than one of the above 5 methods on any given test sample, though not quantitatively comparable, have nearly always been in the same direction.