Influence of dietary nucleotide restriction on bacterial sepsis and phagocytic cell function in mice
A. D. Kulkarni, W. C. Fanslow, D. B. Drath, F. B. Rudolph and C. T. Van Buren
Although enzyme defects in purine metabolism have revealed the importance
of these substrates to maintenance of a normal immune response, the role of
exogenous nucleotides on the cells that mediate the host defense system has
remained largely unexplored. Recent investigations have revealed that
dietary nucleotides are vital to the maintenance of cell-mediated responses
to antigen stimulation. To test the influence of dietary nucleotide
deprivation on resistance to infection, Balb/c mice were maintained on
chow, a nucleotide-free (NF) diet, or an NF diet repleted with adenine,
uracil, or RNA. Mice on the NF diet suffered 100% mortality following
intravenous challenge with Staphylococcus aureus, while chow-fed and RNA-
or uracil-repleted mice demonstrated significantly greater resistance to
this bacterial challenge. Macrophages from mice on the NF diet had
decreased phagocytic activity as measured by uptake of radiolabeled
bacteria compared with mice maintained on the NF diet supplemented with
adenine, uracil, or RNA. No change in S aureus antibody response was noted
on the various diets. Although the mechanism of this suppression of
nonspecific immunity remains unclear, provision of nucleotides to defined
diets appears vital to maintain host resistance to bacterial challenge.