Potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis

BMC Med. 2016 Jun 15:14:89. doi: 10.1186/s12916-016-0635-1.

Abstract

Treatment of multidrug-resistant tuberculosis (MDR-TB) is extremely challenging due to the virulence of the etiologic strains of Mycobacterium tuberculosis (M. tb), the aberrant host immune responses and the diminishing treatment options with TB drugs. New treatment regimens incorporating therapeutics targeting both M. tb and host factors are urgently needed to improve the clinical management outcomes of MDR-TB. Host-directed therapies (HDT) could avert destructive tuberculous lung pathology, facilitate eradication of M. tb, improve survival and prevent long-term functional disability. In this review we (1) discuss the use of HDT for cancer and other infections, drawing parallels and the precedent they set for MDR-TB treatment, (2) highlight preclinical studies of pharmacological agents commonly used in clinical practice which have HDT potential, and (3) outline developments in cellular therapy to promote clinically beneficial immunomodulation to improve treatment outcomes in patients with pulmonary MDR-TB. The use of HDTs as adjuncts to MDR-TB therapy requires urgent evaluation.

Keywords: Host-directed therapies; Immune response; Immunomodulatory agents; Inflammation; Multidrug resistance; Tuberculosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacology*
  • Combined Modality Therapy
  • Humans
  • Immunologic Factors / pharmacology*
  • Mycobacterium tuberculosis / drug effects
  • Tuberculosis, Multidrug-Resistant / drug therapy*

Substances

  • Antitubercular Agents
  • Immunologic Factors