Transfer factors as immunotherapy and supplement of chemotherapy in experimental pulmonary tuberculosis

Abstract

SUMMARYProblems of logistics, compliance and drug resistance point to an urgent need for immunotherapeutic strategies capable of shortening the current six month antibiotic regimens used to treat tuberculosis. One potential immunotherapeutic agent is transfer factors. Transfer factors (TF) are low molecular weight dialysable products from immune cells which transmit the ability to express delayed-type hypersensitivity (DTH) and cell mediated immunity from sensitized donors to nonimmune recipients. In this study we determined the efficiency of TF as immunotherapy to treat experimental tuberculosis. When BALB/c mice are infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance dominated by Th-1 type cytokines plus tumour necrosis factor-alpha (TNF a ) and the inducible isoform of nitric oxide synthase (iNOS), followed by a phase of progressive disease characterized by increasing expression of IL-4, diminished expression of TNF a and iNOS, and low DTH. Animals in this late progressive phase of the disease (day 60) were treated with different doses of TF (one injection per week) obtained from spleen cells when the peak of immune protection in this animal model is reached (day 21), or with different doses of TF from peripheral leucocytes of PPD + healthy subjects. We show here that the treatment with murine or human TF restored the expression of Th-1 cytokines, TNF a and iNOS provoking inhibition of bacterial proliferation and significant increase of DTH and survival. This beneficial effect was dose dependent. Interestingly, murine TF in combination with conventional chemotherapy had a synergistic effect producing significant faster elimination of lung bacteria loads than chemotherapy alone.

The Effect of Transfer Factor as Immunoprotective in Mice Challenged with <i>Mycobacteriu</i>m <i>tuberculosis</i>

“…The peak of immune protection in this animal model reached in day 21. This agree with a study done by Fabre [10] in Mexico, used Transfer Factor as immunotherapy and supplement of chemotherapy in experimental pulmonary tuberculosis [10]. The current study found that the effect of administration of murine transfer factor (TF) on survival of challenged mice was majority (83.3%) comparing with maximum (100%) mortality of the control group, and this result obtained is in accordance with a study done in Mexico 2004 by Fabre (Transfer factors as immunotherapy and supplement of chemotherapy in experimental pulmonary tuberculosis)where they found that the BALB/c mice which were infected via the trachea with Mycobacterium tuberculosis H37Rv and treated with mTF showed a significant 95% survival when compared with the control group, which exhibited 100% mortality.…”

“…Mexican team of investigators have shown that treatment of mice infected with M. tuberculosis with a murine tuberculosis-specific TF restored expression of the Th1 cytokine pattern and resulted in inhibition of bacterial proliferation, significant increase of DTH, and animal survival [10]. The efficiency of TF was highly depended on the dose and, to its source (murine, human or bovine),colostrums is rich in transfer factor.4lifeTransfer Factor, American company is famous and well known in the production of TF.…”

Immunotherapy with Dialyzable Leukocyte Extracts Containing Transfer Factor

“…The specific TF was produced from tuberculous BALB/c mice following intra-tracheal infection. The treatment with TF leads to restoration of the expression of the Th1 cytokine pattern, whereas the increase of delayed type hypersensitivity leads to inhibition of bacterial proliferation and animal survival [62].…”

Dialysable leukocyte extracts in immunotherapy

“…They are related to restoration of the expression of the Th1 cytokine pattern, increase in DTH, leading to inhibition of bacterial proliferation and better animal survival. [60] TF preparations have also been tested against M. leprae, M. fortuitum pneumonia and M. xenori (as mentioned in [27]). …”