Effect of 6-Mercaptopurine on Endotoxin Tolerance*

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Abstract
Endotoxin tolerance was induced in rabbits by 7 daily intravenous injections of Escherichia coli endotoxin. Half of the animals also received 6-mercaptopurine, whereas the rest were given a control solution. Antibody response of the 6-mercaptopurine (6-MP)-treated animals was significantly suppressed. Furthermore, 19 S macroglobulin levels were also lower in the drug-treated group. Despite the differences in antibody levels, 6-MP-treated animals, when given a range of challenge doses of endotoxin, were as tolerant as control animals. Similarly, "antibody poor" plasma (i.e., from 6-MP- treated animals) passively transferred febrile tolerance as well as did "antibody rich" (control) plasma. These findings are not consistent with circulating antibody being the sole, or even major, factor responsible for endotoxin tolerance.