Alcohol and susceptibility to tuberculosis

Abstract

Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious agent (Flynn and Bloom 1996). Mycobacterium tuberculosis, the agent responsible for TB, is transmitted when a person inhales microscopic airborne particles containing the organism (i.e., droplet nuclei) coughed up by someone with active TB disease, although prolonged exposure usually is necessary before an infection becomes established. Initially M. tuberculosis attacks the lung, where immune cells (i.e., macrophages and lymphocytes) battle the infection. In the absence of adequate immunity, however, the bacteria ingested by macrophages continue to multiply within these immune cells, and characteristic lesions called tubercles eventually form in the lungs. Among other symptoms, people with active TB develop a bloody cough, fatigue, and difficulty breathing. TB can affect any organ system or develop into systemic infection (i.e., miliary TB) when infected cells spread from the lungs and disseminate through the bloodstream. No effective vaccination against TB currently exists, but 6 to 9 months of treatment with multiple antituberculous drugs will cure most TB patients who complete the course of therapy. Sociological studies show that TB is more prevalent in low-income, densely populated housing areas-settings often associated with high rates of alcoholism.' Numerous studies also have noted a direct association between alcoholism and pulmonary tuberculosis (Jacobson 1992). Such apparent susceptibility to TB infection among alcoholics, especially those who are homeless or indigent, can be attributed both to biological and to social and behavioral factors. Biological Factors Although approximately one-third of the world's population is infected with M. tuberculosis, only about 10 percent will experience either acute or reactivated disease (Flynn and Bloom 1996). Clearly, the body's immune system is quite capable of controlling M. tuberculosis in most cases. Any illness or condition associated with an impaired immune system, however, can increase the likelihood of developing active TB. In particular, numerous animal studies have confirmed that the body's control of M. tuberculosis infection resides in its ability to mobilize macrophages and lymphocytes against invading organisms (i.e., cell-mediated immunity) (Dunlap and Briles 1993). Because alcohol use significantly inhibits cell-mediated immunity, it compromises the body's immune defense. Thus, alcoholism-along with other diseases associated with impaired cell-mediated immunity (e.g., HIV infection)-increases a person's susceptibility to active TB infection as well as reactivation of latent disease (Flynn and Bloom 1996). Researchers do not know, however, whether alcohol consumption itself or the liver damage and malnutrition often associated with alcoholism are primarily responsible for the impaired immunity of alcoholics. Investigators studying mechanisms by which alcohol predisposes people to TB recently have focused special attention on the specific immune system components participating in the body's defense against M. tuberculosis and related mycobacteria. Alcohol use has been found to hinder the body's antimycobacterial defense on multiple levels, including through impaired macrophage response, altered levels of the proteins that act as intercellular mediators (i.e., cytokines), and a disturbed balance between the two basic types of acquired immunity: cell-mediated immunity and immunity provided by circulating antibodies (i.e., humoral immunity). Each of these interrelated consequences is discussed in the sections that follow. Impaired Macrophage Response. Macrophage activation is considered essential for local containment and destruction of mycobacteria (including M. tuberculosis) and other invasive microorganisms. Thus, macrophage activity is the hallmark of resistance to TB (Flynn and Bloom 1996). These immune system cells (along with the monocytes that give rise to them) play a key role in directly presenting the chemical identifiers that stimulate an immune response (i. …