In vivo and in vitro studies of a novel cytokine, interleukin 4δ2, in pulmonary tuberculosis

Keertan Dheda, Jung Su Chang, Ronan A.M. Breen, Louise U. Kim, Jamanda A. Haddock, Jim F. Huggett, Margaret A. Johnson, Graham A.W. Rook, Alimuddin Zumla

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)


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 4δ2 (IL-4δ2), a splice variant and inhibitor of IL-4. Objective: To study levels of mRNA encoding IL-4 and IL-482, and their relationship to treatment and clinical parameters, in cells from lung lavage and blood from patients with pulmonary tuberculosis. Methods: IL-482, IFN-γ, 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-4δ2 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-4δ2 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/INF-γ ratio and sCD30 (p < 0.005). After chemotherapy, IL-4 mRNA levels remained unchanged, whereas IL-4δ2 increased in parallel with IFN-γ (p < 0.05). Sonicates of Mycobacterium tuberculosis upregulated expression of IL-4 relative to IL-4δ2 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-482 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.

Original languageEnglish
Pages (from-to)501-508
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number4
Publication statusPublished - Aug 15 2005
Externally publishedYes


  • Cytokines
  • Human
  • Interleukin 4
  • Th1/Th2 cells
  • Tuberculosis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Pulmonary and Respiratory Medicine


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