EFFECTS OF PROTEIN-CALORIE MALNUTRITION ON TUBERCULOSIS IN MICE

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.