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Rats infected with virulent Diplococcus pneumoniae developed a significant increase in the rate of incorporation of labelled orotate into hepatic RNA when compared with pair-fed controls inoculated with heat-killed organisms. The finding was readily detected in rats raised on either a low-protein diet (6% casein) or a diet containing adequate amounts of protein (18% casein). The increase in hepatic RNA synthesis was observed by 12h and was maximal by 16-20h after inoculation with the D. pneumoniae. Most of the infection-related increase in RNA synthesis was associated with the bound ribosomal RNA fraction of the liver. A small but less significant increase was observed in the synthesis of free ribosomal RNA. The increased synthesis of RNA in the liver of infected rats resulted in a marked elevation of the liver RNA/DNA ratio, the major increase being observed in concentration of bound ribosomal RNA fraction. When followed sequentially, the infection-related increase in synthesis of hepatic RNA was preceded by a flux of amino acids into liver and was followed by elevated synthesis rates of serum globulin proteins. These findings suggest that the infectious process was able to regulate hepatic RNA synthesis by altering the rate of transcription of new RNA. This mechanism was stimulated even in rats that had been severely depleted of body protein and amino acids by feeding them on a low-protein diet. The infection-related stimulation of liver RNA and protein synthesis thus appeared to take place at the expense of other body proteins.

The effect of protein-free and starvation diets on the migration of cells from the crypts onto and up the villi of the rat ileum was studied. Rats starved for 3, 7, or 10 days or fed a protein-free diet (PFD) for 3, 7, or 11 wk were injected with thymidine-(3)H and sacrificed at timed intervals. The time required for the labeled cells to first appear on the villi of experimental animals was longer than in the controls. This was the result of an elongated cycle in the protein-depleted animals and a lengthening of the maturation period in both the starved and protein-depleted animals. Determination of the distance which labeled cells had migrated up the villi in control and experimental animals, after thymidine-(3)H injection, indicated that cells in animals starved for 7 days migrated more rapidly than those in the fed controls, while those of 10-day starved animals moved more slowly. The cells of animals fed PFD for 3 wk migrated up the villi more rapidly, those of animals depleted for 7 wk migrated at the same time rate, and those of 11-wk PFD animals migrated more slowly than the fed controls. There is apparently no correlation between the cell cycle time in the crypt cells and the rate of migration of cells up the villus.

The concentration of 21 individual free amino acids in serum, liver, and skeletal muscle was determined in rats during the incubation, acute illness, and terminal stages of experimental infection with Diplococcus pneumoniae. By 4 hr after subcutaneous inoculation with bacteria, the concentration of total and many individual free amino acids in serum, liver, and muscle was significantly decreased in comparison to findings in noninfected, pair-fed control rats. By use of a nonmetabolizable amino acid analogue (cycloleucine), it was possible to detect a flux of amino acids from muscle to liver in the infected rat. The endogenous amino acids which moved to the liver were rapidly utilized for the synthesis of serum proteins.