• Tuberculosis;
  • IL-4;
  • Fibrosis;
  • Immunopathology;
  • TNF-α


In BALB/c mice, as in man, progressive pulmonary tuberculosis is accompanied by increasing expression of IL-4. Therefore we have used BALB/c mice with disrupted IL-4 genes (IL-4–/–) to investigate the role of IL-4 in pulmonary tuberculosis, with particular emphasis on the toxicity of TNF-α and on fibrosis, both of which are neglected aspects of human tuberculosis. Delayed-type hypersensitivity (DTH) sites in IL-4+/+ mice were sensitive to the toxicity of locally injected TNF-α, whereas DTH sites in IL-4–/– mice were not. However, intravenous administration of IL-4 to IL–4–/– mice restored the sensitivity of the DTH sites to pro-inflammatory effects of TNF-α. In late disease, the lungs of IL-4+/+ mice expressed low IFN-γ, but high TGF-β and IL-4, correlating with fibrosis, detected as a high hydroxyproline content. In contrast, TGF–β peaked 7 days after infection in the lungs of the IL-4–/– mice, and then fell to very low levels in the late disease, while IFN-γ remained high. Accordingly, hydroxyproline content was reduced in infected IL-4–/– mice compared to IL-4+/+ controls. In conclusion, the findings suggest that IL-4 has modestly detrimental effects on the antibacterial efficacy of the Th1 response, and larger effects on the toxicity of TNF-α, and on fibrosis.