Effects of endotoxin on the histology of intact and athymic mice infected with Plasmodium vinckei petteri.

Apparently healthy intact and athymic mice with low to moderate parasitaemias of P. vinckei petteri are very susceptible to the harmful effects of Endotoxin (LPS). The histological changes seen in such mice after injection of a small dose of LPS closely resemble those seen in mice terminally infected with this parasite. Thus the onset of pathology could be hastened by giving a little LPS. Both groups of intact mice showed foci of hepatic necrosis, severe necrosis in the thymus, and light to moderate necrosis in the germinal centres of the splenic white pulp and Peyer's patches. In contrast liver necrosis was seen in very few of the terminally ill athymic mice and in none of the athymic mice given LPS. Our results imply that the lesions produced by LPS in the liver and lymphoid organs of apparently healthy mice with low to moderate parasitaemias would have eventually developed, without the help of extrinsic LPS, as the parasitaemia rose further and the infection ran its normal fatal course. This would be consistent with an intrinsic LPS-like activity in these terminally infected mice. One possible contributor to the liver necrosis seen in this infection is a T-dependent mediator reported to block enzyme induction. Any proposal for the mechanism of this damage must explain its rarity in athymic mice, its induction by LPS in intact but not athymic mice, and host differences in parasite density at which it occurs.