J. Chan et al., EFFECTS OF PROTEIN-CALORIE MALNUTRITION ON TUBERCULOSIS IN MICE, Proceedings of the National Academy of Sciences of the United Statesof America, 93(25), 1996, pp. 14857-14861
Infectious diseases and malnutrition represent major burdens afflictin
g millions of people in developing countries, Both conditions affect i
ndividuals in industrialized nations, particularly the aged, the HIV-i
nfected, and people with chronic diseases, While malnutrition is known
to induce a state of immunodeficiency, the mechanisms responsible for
compromised antimicrobial resistance in malnourished hosts remain obs
cure, In the present study, mice fed a 2% protein diet and developing
protein calorie malnutrition, in contrast to cell-nourished controls r
eceiving a 20% protein diet, rapidly succumbed to infection with Mycob
acterium tuberculosis, Malnourished mice exhibited a tissue-specific d
iminution in the expression of interferon gamma, tumor necrosis factor
or, and the inducible form of nitric oxide synthase in the lungs, but
not the liver, The expression of these molecules critical to the prod
uction of mycobactericidal nitrogen oxides was depressed in malnourish
ed animals in the lungs specifically at early times (<14 days) after i
nfection, At later times, levels of expression became comparable to th
ose in well-nourished controls, although the bacillary burden in the m
alnourished animals continued to rise, Nevertheless, urinary and serum
nitrate contents, an index of total nitric oxide (NO) production in v
ivo, were not detectably diminished in malnourished, mycobacteria-infe
cted mice. In contrast to the selective and early reduction of lymphok
ines and the inducible form of nitric oxide synthase in the lung, a ma
rked diminution of the granulomatous reaction was observed in malnouri
shed mice throughout the entire course of infection in all tissues exa
mined (lungs, liver, and spleen), Remarkably, the progressively fatal
course of tuberculosis observed in the malnourished mice could be reve
rsed by restoring a full protein (20%) diet, The results indicate that
protein calorie malnutrition selectively compromises several componen
ts of the cellular immune response that are important for containing a
nd restricting tuberculous infection, and suggest that malnutrition-in
duced susceptibility to some infectious diseases can be reversed or am
eliorated by nutritional intervention.