Effects of a protein deprived diet on the hepatotoxicity, and the DNA synthetic, mitogenic, and immunological actions of microbial lipopolysaccharides in the rat.

Rats fed an 18% casein (Cs) or a protein deprived diet (PD) for 8 weeks received injections of Escherichia coli lipopolysaccharides (LPS) in both hind foot pads. While these injections were tolerated in Cs rats, about 50% of PD rats died after 1 or 2 days as a result of a massive necrosis of the liver. To a large extent these lesions were prevented by cortisone. Three days after injection of LPS, Cs rats exhibited a hypertrophy of the popliteal lymph nodes (PLN) and spleen, as well as a drastic increase in DNA synthesis in DNA synthesis in the PLN. Mitotic indices did not increase. The DNA synthetic responses to PLN in the surviving PD rats were much lower than in Cs animals, but a sharp rise in DNA synthesis and mitotic activity occurred in the spleen. The comparison with the effects of LPS in cortisone-treated rats showed that both cortisone-sensitive and -resistant cells participated in PLN activation in rats fed both diets, but that only cortisone-resistant lymphocytes entered mitosis in the spleens of PD rats. LPS also provoked a sharp drop in both DNA synthesis and mitosis in the thymus, probably due to a stress effect, since only cortisone-sensitive thymocytes were involved. In a second experimental series, immunological tests (Rosette-forming cells, Plaque-forming cells, serum hemagglutinin titers) were performed 7 days after intraperitoneal injection of LPS. The responses were not significantly different in Cs and PD rats. This is in contrast with the protein deficiency-induced depression of thymus-dependent humoral immunity.