IMMUNOTHERAPY FOR MDR-TB (MULTI-DRUG-RESISTANT TUBERCULOSIS)-ITS FEASIBILITY

Abstract

MDR-TB is known to be man-made-disease. Inappropriate treatment of tuberculosis is responsible for the development of MDR-TB.
MDR-TB is often accompanied with the immunosuppression of the host. Given that we are unable to develop another potent anti-TB drug in near future, immunotherapy directed at combating immunosuppression and enhancing the host's own immune response is an attractive approach to supplement conventional chemotherapy for MDR-TB.
Patients with AIDS and patients with abnormalities of macrophage function have frequent problems with TB. This is suggesting that the host defenses involved in protection against mycobacteria include T-cell and monocyte/macrophage functions. That is cell-mediated immunity.
Diverse cytokines are known to play an important role in anti-TB cell-mediated immunity, including IL-2, IL-12, IL-18 and IFN-γ. Various animal experiments are indicating that administration of these cytokine (s) did recover the suppressed immunity and rescued the host from death by tuberculous infection. However, we have to keep it in mind that the results obtained from animal model of mycobacterial infection on the study of pathogenesis and immune responses in TB is not always applicable to the understanding of human TB. Clinical trial of inhalation therapy with IFN-γ showed some improvement for drug-resistant TB. Cytokine treatment, however, often gave some deleterious side effects such as high fever, malaise, general edema and even the death of the host.
Clinical trials with M. vaccae have been extensively conducted by UK group. The mechanisms underlying its possible therapeutic action remain to be clarified, but when administered at an appropriate dose, it has been shown to elicit a strong Thl immune response.
From the practical view point of immunotherapy for TB, surrogate markers of disease eradication and protective immunity are urgently required. Such markers would facilitate clinical trials by providing early evidence that test compounds or vaccines are effective.
Even during the era when no potent chemotherapeutic agents were available, one third of the patients with TB survived the disease and enjoyed the entire lives. Then the question is what determines the alternative: survival or death following development of drug-resistant TB. Is it host immune responsiveness or virulence of the microbe, or both? Clearly much more work seems required before we are able to find some definite means to conquer MDR-TB in human.