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Clinical and Vaccine Immunology, August 2008, p. 1165-1170, Vol. 15, No. 8
1071-412X/08/$08.00+0     doi:10.1128/CVI.00084-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Differential Expression of Interleukin-4 (IL-4) and IL-4{delta}2 mRNA, but Not Transforming Growth Factor Beta (TGF-β), TGF-βRII, Foxp3, Gamma Interferon, T-bet, or GATA-3 mRNA, in Patients with Fast and Slow Responses to Antituberculosis Treatment{triangledown}

Joel Fleury Djoba Siawaya,1* Nchinya Bennedict Bapela,1 Katharina Ronacher,1 Nulda Beyers,2 Paul van Helden,1 and Gerhard Walzl1

Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa,1 Department of Pediatrics and Desmond Tutu TB Centre, Stellenbosch University, Cape Town, South Africa2

Received 19 February 2008/ Returned for modification 14 April 2008/ Accepted 13 June 2008

This study investigated interleukin-4 (IL-4), IL-4{delta}2, transforming growth factor beta (TGF-β), TGF-βRII, Foxp3, GATA-3, T-bet, and gamma interferon (IFN-{gamma}) transcription in peripheral blood samples of adult pulmonary tuberculosis patients prior to and after 1 week of therapy. Twenty patients with positive results for sputum culture for Mycobacterium tuberculosis were enrolled and treated with directly observed short-course antituberculosis chemotherapy. Early treatment response was assessed. At the end of the intensive phase of treatment (month 2), 12 patients remained sputum culture positive (slow responders) and 8 converted to a negative culture (fast responders). Only the expression levels of IL-4 (4-fold decrease) and IL-4{delta}2 (32-fold increase) changed significantly during the first week of therapy in the 20 patients. No baseline differences were present between the responder groups, but fast responders had significantly higher IL-4 transcripts than slow responders at week 1. Fast responders showed a 19-fold upregulation and slow responders a 47-fold upregulation of IL-4{delta}2 at week 1. Only slow responders also showed a significant decrease in IL-4 expression at week 1. There were no significant differences in expression of TGF-β, TGF-βRII, Foxp3, IFN-{gamma}, and GATA-3 between the groups. These data show that differential IL-4-related gene expression in the early stage of antituberculosis treatment accompanies differential treatment responses and may hold promise as a marker for treatment effect.

* Corresponding author. Mailing address: Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Cape Town 7505, South Africa. Phone: 00 27 21 938 9402. Fax: 00 27 21 938 9476. E-mail: joe{at}sun.ac.za

{triangledown} Published ahead of print on 25 June 2008.

Clinical and Vaccine Immunology, August 2008, p. 1165-1170, Vol. 15, No. 8
1071-412X/08/$08.00+0     doi:10.1128/CVI.00084-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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