Immunological and endocrinological characteristics of tuberculosis that provide opportunities for immunotherapeutic intervention

Novartis Found Symp. 1998;217:73-87; discussion 87-98. doi: 10.1002/0470846526.ch6.

Abstract

Immunity to tuberculosis requires a T helper 1 (Th1) response which can be compromised by excessive release of inflammatory cytokines or Th2 activity. Environmental saprophytes can protect against tuberculosis by inducing Th1 recognition of the common antigens, or make mice more susceptible to tuberculosis than unimmunized controls by evoking a Th2 response. A mixed Th1 + Th2 response increases the local toxicity of tumour necrosis factor alpha (TNF-alpha). Some saprophytes are potent immunogens. A killed preparation of Mycobacterium vaccae can cause systemic activation of spontaneously Th1 cytokine-secreting cells in humans, and can non-specifically suppress pre-existing IgE formation and interleukin 5 (IL-5) production in murine models of allergy. These effects, and the Th2-inducing effects of other species, may explain the variable efficacy of Bacillus Calmette-Guérin, and suggest the need for new approaches to the screening of vaccines before trial in humans. The balance of Th1 to Th2 and the function of inflammatory cytokines are also regulated by cortisol. Glucocorticoid metabolism is abnormal in tuberculosis, suggesting overactivity of 11-beta-hydroxysteroid reductase enzymes. The reductase activity of these enzymes is enhanced by TNF-alpha and IL-1 beta. The roles of Th2, inflammatory cytokines, common antigens and changes in cortisol metabolism suggest several strategies for immunotherapy, and several sites where genetic polymorphisms may affect susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • BCG Vaccine / immunology
  • Clinical Trials as Topic
  • Endocrine Glands / metabolism*
  • Glucocorticoids / metabolism*
  • Immunotherapy
  • Th1 Cells
  • Th2 Cells
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / therapy*
  • Tumor Necrosis Factor-alpha

Substances

  • BCG Vaccine
  • Glucocorticoids
  • Tumor Necrosis Factor-alpha