This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200502-278OCv1 172/4/501    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dheda, K. Articles by Zumla, A. Search for Related Content PubMed PubMed Citation Articles by Dheda, K. Articles by Zumla, A.

In Vivo and In Vitro Studies of a Novel Cytokine, Interleukin 42, in Pulmonary Tuberculosis

Centre for Infectious Diseases and International Health, Royal Free and University College Medical School; and Departments of Thoracic and HIV Medicine and Radiology, Royal Free Hospital NHS Trust, London, United Kingdom

Correspondence and requests for reprints should be addressed to Prof. Graham A. W. Rook, B.A., M.B., B. Chir., M.D., Centre for Infectious Diseases and International Health, Royal Free and University College Medical School, 46 Cleveland Street, London W1T 4JF, United Kingdom. E-mail: g.rook{at}ucl.ac.uk

Rationale: Tuberculosis progresses despite potent Th1 responses. A putative explanation is the simultaneous presence of a subversive Th2 response. However, interpretation is confounded by interleukin 42 (IL-42), a splice variant and inhibitor of IL-4. Objective: To study levels of mRNA encoding IL-4 and IL-42, and their relationship to treatment and clinical parameters, in cells from lung lavage and blood from patients with pulmonary tuberculosis. Methods: IL-42, IFN-, IL-4, and soluble CD30 (sCD30) levels were measured by polymerase chain reaction and relevant immunoassays in 29 patients and matched control subjects lacking responses to tuberculosis-specific antigens. Results: mRNA levels for IL-4 and IL-42 were elevated in unstimulated cells from blood and lung lavage of patients versus control subjects (p < 0.005). In control subjects, there were low basal levels of IL-4 and IL-42 mRNA expressed mainly by non–T cells (p < 0.05). However, in patients, there were greater levels of mRNA for both cytokines in both T- and non–T-cell populations (p < 0.05 compared with control subjects). Radiologic disease correlated with the IL-4/IFN- ratio and sCD30 (p < 0.005). After chemotherapy, IL-4 mRNA levels remained unchanged, whereas IL-42 increased in parallel with IFN- (p < 0.05). Sonicates of Mycobacterium tuberculosis upregulated expression of IL-4 relative to IL-42 in mononuclear cell cultures from patients (p < 0.05). Conclusions: A Th2-like response, prominent in T cells and driven by tuberculosis antigen, is present in tuberculosis and modulated by treatment, suggesting a role for IL-4 and IL-42 in the pathogenesis of tuberculosis and their ratio as a possible marker of disease activity. The specific antigens inducing the IL-4 response require identification to facilitate future vaccine development strategies.

Key Words: cytokines • human • interleukin 4 • Th1/Th2 cells • tuberculosis

This article has been cited by other articles:

				K Dheda, J-S Chang, S Lala, J F Huggett, A Zumla, and G A W Rook Gene expression of IL17 and IL23 in the lungs of patients with active tuberculosis Thorax, June 1, 2008; 63(6): 566 - 568. [Full Text] [PDF]

				A. Demissie, L. Wassie, M. Abebe, A. Aseffa, G. Rook, A. Zumla, P. Andersen, T. M. Doherty, and the VACSEL Study Group The 6-kilodalton early secreted antigenic target-responsive, asymptomatic contacts of tuberculosis patients express elevated levels of interleukin-4 and reduced levels of gamma interferon. Infect. Immun., May 1, 2006; 74(5): 2817 - 2822. [Abstract] [Full Text] [PDF]

				W. W. Yew and C. C. Leung Update in tuberculosis 2005. Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 491 - 498. [Full Text] [PDF]

				J.-S. Chang, J. F. Huggett, K. Dheda, L. U. Kim, A. Zumla, and G. A. W. Rook Myobacterium tuberculosis Induces Selective Up-Regulation of TLRs in the Mononuclear Leukocytes of Patients with Active Pulmonary Tuberculosis. J. Immunol., March 1, 2006; 176(5): 3010 - 3018. [Abstract] [Full Text] [PDF]