Significance of TNF in the Immune Response against Tuberculosis (pp. 93-112)
$100.00
Authors: (Guadalupe Garc¨ªa-Elorriaga, Guillermo del Rey-Pineda, Hospital de Infectolog¨ªa, Centro M¨¦dico Nacional La Raza (CMNR), Instituto Mexicano del Seguro Social (IMSS), M¨¦xico, and others)
Abstract: Alveolar macrophages (AM) are the first cell line of defense against
Mycobacterium tuberculosis (Mtb); they possess different effector
mechanisms controlling the growth of mycobacteria. AM also secrete
cytokines, such as tumor necrosis factor (TNF) that in turn, induces nitric
oxide (NO) production, one of the main effector mechanisms against Mtb.
TNF is also produced by T lymphocytes playing an active role in infection control, the expression of inducible NO synthase (iNOS) and
cell migration, acting synergistically with interferon gamma, fomenting
the expression of adhesion molecules, chemokines and their receptors, as
well as localizing Mtb in tissues and promoting the formation,
organization and preservation of granulomas. Classical apoptosis of Mtbinfected
macrophages is largely beneficial to the host and detrimental to
the infecting bacilli. The expression of TNF in tuberculosis (TB) and
other diseases of infectious origin may vary from one individual to
another and between populations. These variations can be partly
explained by polymorphisms in the gene promoter region. TNF plays a
major role in host defense in both active and latent phases of infection. It
is a key regulator of inflammation per se and abnormalities in its
functional regulation play a major role in the development of chronic
inflammatory diseases (i.e. rheumatoid arthritis) and infections. Thus,
TNF-neutralizing therapies have led to excellent clinical, biochemical and
radiological improvements in the treatment of those diseases, but
concerns persist over major adverse effects given the central role of TNF
in host defense mechanisms, especially against TB. There is a close
temporal drug-effect relation in TB development when using these
agents, especially infliximab. Guidelines proposing the screening of latent
tuberculosis infection (LTBI) risk before initiation of infliximab must be
implemented in every country and in accordance with their local
epidemiology profile. With further research, a TNF-targeting drug with
limited side effects, including less interference with granuloma formation,
should be developed.
