In vivo and in vitro studies of a novel cytokine, interleukin 4delta2, in pulmonary tuberculosis

Am J Respir Crit Care Med. 2005 Aug 15;172(4):501-8. doi: 10.1164/rccm.200502-278OC. Epub 2005 May 18.


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 4delta2 (IL-4delta2), a splice variant and inhibitor of IL-4.

Objective: To study levels of mRNA encoding IL-4 and IL-4delta2, and their relationship to treatment and clinical parameters, in cells from lung lavage and blood from patients with pulmonary tuberculosis.

Methods: IL-4delta2, IFN-gamma, 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-4delta2 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-4delta2 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-gamma ratio and sCD30 (p < 0.005). After chemotherapy, IL-4 mRNA levels remained unchanged, whereas IL-4delta2 increased in parallel with IFN-gamma (p < 0.05). Sonicates of Mycobacterium tuberculosis upregulated expression of IL-4 relative to IL-4delta2 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-4delta2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bronchoalveolar Lavage Fluid / chemistry
  • Case-Control Studies
  • Cell Separation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Gene Expression
  • Humans
  • In Vitro Techniques
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / immunology*
  • Male
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Tuberculosis, Pulmonary / immunology*


  • RNA, Messenger
  • Interleukin-4