Effects of protein calorie malnutrition on tuberculosis in mice

Abstract

Infectious diseases and malnutrition represent major burdens aff licting millions of people in developing countries. Both conditions affect individuals in industrialized nations, particularly the aged, the HIV-infected, 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 obscure. In the present study, mice fed a 2% protein diet and developing protein calorie malnutrition, in contrast to well-nourished controls receiving a 20% protein diet, rapidly succumbed to infection with Mycobacterium tuberculosis. Malnourished mice exhibited a tissue-specific diminution in the expression of interferon ␥, tumor necrosis factor ␣, and the inducible form of nitric oxide synthase in the lungs, but not the liver. The expression of these molecules critical to the production of mycobactericidal nitrogen oxides was depressed in malnourished animals in the lungs specifically at early times (<14 days) after infection. At later times, levels of expression became comparable to those in well-nourished controls, although the bacillary burden in the malnourished animals continued to rise. Nevertheless, urinary and serum nitrate contents, an index of total nitric oxide (NO) production in vivo, were not detectably diminished in malnourished, mycobacteria-infected mice. In contrast to the selective and early reduction of lymphokines and the inducible form of nitric oxide synthase in the lung, a marked diminution of the granulomatous reaction was observed in malnourished mice throughout the entire course of infection in all tissues examined (lungs, liver, and spleen). Remarkably, the progressively fatal course of tuberculosis observed in the malnourished mice could be reversed by restoring a full protein (20%) diet. The results indicate that protein calorie malnutrition selectively compromises several components of the cellular immune response that are important for containing and restricting tuberculous infection, and suggest that malnutritioninduced susceptibility to some infectious diseases can be reversed or ameliorated by nutritional intervention.

Markers of Disease Evolution: The Case of Tuberculosis

“…This last assumption is enough to reproduce the patterns of (high) incidence of active-TB over the past 150 years! Malnutrition (Chan et al 1996, Raloff 1996 and other factors that weaken the body immune's response are known to increase the risk of developing active-TB. Hence, it is not a stretch to assume that increases in the average standard of living actually streghthens the average population immune-response to diseases like TB.…”

Influence of nutritional state on the progression and severity of mycobacteriosis in striped bass Morone saxatilis

“…Much work in this area has focused on the association of protein calorie malnutrition (PCM) and reduced immune function. Chan et al (1996) demonstrated that mice receiving a reduced protein diet (2%) rapidly succumbed to tuberculosis accompanied by a reduced expression of interferon γ, tumor necrosis factor ά , and nitric oxide synthase in the lungs. These cytokines, as well as interleukin-1 (IL1), interleukin-4 (IL4), and transforming growth factor β are critical to the production of nitrous oxides and other reactive nitrogen intermediates, which are used by phagocytes to kill pathogens (Plouffe et al 2005).…”

Unchanged interleukin 6 level of protein and energy restricted goats during late gestation: the role of elevated blood nitric oxide

“…In previous experiments, there have been variable inflammatory immune responses to malnutrition. Decreased plasma TNFa production has been reported in rodent models of protein-energy malnutrition (Chan et al 1996, Schaffer et al 1997, Anstead et al 2001, but increased plasma IL6 concentration has been observed in malnourished patients (Malave et al 1998, Johann-Liang et al 2000, de Martino et al 2000. In addition, maternal dietary protein restriction decreased NO synthase (NOS) in endometrium and placenta of pigs during early gestation (Wu et al 1998).…”