Adjunctive Immunotherapy for Drug-Resistant Tuberculosis
The fear of the epidemic of tuberculosis due to multi-drug resistant strains
has prompted scientists to seek new drugs complementing conventional
ones introduced in the early fifties.
While new anti-tuberculosis drugs are being sought,
immunotherapy in conjunction with the standard chemotherapy points
to another potentially useful solution.
The merit of such adjunctive immunotherapy in multi-drug resistance
cases has been demonstrated in some clinical studies.
As host immune defense is a critical factor in the pathogenicity
immunotherapy should play an important role in disease prevention
Cytokines refer to an array of relatively low molecular weight,
pharmacologically active proteins that are secreted by one cell and can
alter either its own functions (autocrine effect) or those of
adjacent cells (paracrine effect).
Among the cytokine group are a large number of interleukins
plus growth and colony-stimulating factors. Interleukin refers to
a group of well-characterized cytokines that are
produced by leukocytes and other cell types and are equipped with a wide
spectrum of functional activities
related to inflammatory and immune mechanisms.
Cytokines such as TNF-alpha may enter the circulation
and have a systemic effect.
Cytokine therapy for multi-drug resistant tuberculosis has produced
some successes (ref. 1):
IFN-gamma aerosol: rapid sputum smear conversion but no cultural conversion
IFN-gamma subcutaneous: 2 cures. 1 improvement, 2 unchanged
IL-2 intradermal: rapid reduction in sputum smears with clinical improvement
The anti-inflammatory and immunomodulatory effects of thalidomide have
led scientists to explore its clinical therapeutic values.
Thalidomide is now being considered as a potential treatment for
Thalidomide affects cytokine production and T lymphocyte proliferation.
It appears that
thalidomide suppresses TNF-alpha production by macrophages and thereby
reduces inflammatory response. Thalidomide elevates the IFN-gamma level
and modulates several other cytokines as well, noteworthily, IL-2 and IL-12.
Thalidomide costimulates T lymphocytes, with greater effect on CD8+
than CD4+ T cells. This finding is important since CD8+ T cells have been
shown contributory to the protective immune response to tuberculosis
The clinical application of
thalidomide as part of standard tuberculosis therapy
is inconclusive amid variability among reports.
However, thalidomide has been shown to be an effective adjuvant for tuberculosis
patients complicated with severe inflammatory reaction or wasting conditions.
S.M. Holland. 2000.
Adjunctive Immunotherapy (Interferon - g) for
Difficult-to-Treat Infections Including Mycobacterial Disease.