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

SUMMARY Problems 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...

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Published in:	Clinical and experimental immunology Vol. 136; no. 2; pp. 215 - 223
Main Authors:	FABRE, R. A., PÉREZ, T. M., AGUILAR, L. D., RANGEL, M. J., ESTRADA‐GARCÌA, I., HERNÁNDEZ‐PANDO, R., ESTRADA PARRA, S.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Science Ltd 01-05-2004 Blackwell Oxford University Press Blackwell Science Inc
Subjects:	Adjuvants, Immunologic - administration & dosage Animal Studies Animals Antitubercular Agents - therapeutic use Bacterial diseases Bacterial diseases of the respiratory system Biological and medical sciences Enzyme-Linked Immunosorbent Assay - methods experimental tuberculosis Human bacterial diseases Hypersensitivity, Delayed - immunology immunotherapy Immunotherapy, Active - methods Infectious diseases Interleukin-4 - genetics Interleukin-4 - immunology Male Medical sciences Mice Mice, Inbred BALB C Models, Animal Mycobacterium tuberculosis Nitric Oxide Synthase - metabolism Nitric Oxide Synthase Type II Reverse Transcriptase Polymerase Chain Reaction Skin - immunology transfer factor Transfer Factor - administration & dosage Transfer Factor - immunology Tuberculosis, Pulmonary - drug therapy Tuberculosis, Pulmonary - immunology Tuberculosis, Pulmonary - therapy Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - immunology Antineoplastic agent Lung disease Immunopathology Respiratory disease transfer factor immunotherapy experimental tuberculosis Pulmonary tuberculosis Mycobacterial infection Infection Chemotherapy Immunology Treatment Immunotherapy Bacteriosis Transfer
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Summary:	SUMMARY Problems 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 (TNFα) 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 TNFα 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, TNFα 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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0009-9104 1365-2249
DOI:	10.1111/j.1365-2249.2004.02454.x