CVI Accepts, published online ahead of print on 25 June 2008

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Clin. Vaccine Immunol. doi:10.1128/CVI.00084-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Differential expression of IL-4 and IL-42, but not TGF-, TGF-RII, FOXP3, IFN-, T-bet or GATA-3 mRNA in Fast and Slow Responders to Anti-tuberculosis Treatment

Joel Fleury Djoba Siawaya, Nchinya Bennedict Bapela, Katharina Ronacher, Nulda Beyers, Paul van Helden, and Gerhard Walzl

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, South Africa; Department of Pediatrics/Desmond Tutu TB Centre, Stellenbosch University

This study investigated L-4, IL-42, TGF-, TGF-RII, Foxp3, GATA-3, T-bet and IFN- transcription in peripheral blood of adult, pulmonary tuberculosis patients prior to and after one week of therapy. 20 patients with positive sputum culture for M. tuberculosis were enrolled and treated with directly observed short course anti-tuberculosis 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 eight converted to a negative culture (fast responders). Only expression levels of IL-4 (4-fold decrease) and IL-42 (32-fold increase) changed significantly during the first week of therapy in the 20 patients. No baseline differences were present between responder groups but fast responders had significantly higher IL-4 transcripts than slow responders at week one. Fast responders had a 19-fold and slow responders a 47-fold up-regulation of IL-42 at week one. Slow responders only also showed a significant decrease in IL-4 expression at week one. There were no significant differences in the expression of TGF-beta, TGF-beta RII, Foxp3, IFN- and GATA-3 between the groups. These data show that differential IL-4 related gene expression in the early stage of anti-tuberculosis treatment accompanies differential treatment responses and may hold promise as marker for treatment effect.

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