Interleukin-18 expression by alveolar epithelial cells type II in tuberculosis and sarcoidosis

FEMS Immunol Med Microbiol. 2006 Feb;46(1):30-8. doi: 10.1111/j.1574-695X.2005.00013.x.


The aims of the present study were to characterize the localization of interleukin-18 (IL-18) expression in lung tissue specimens from patients with pulmonary tuberculosis, sarcoidosis and controls, and to determine whether human alveolar epithelial cells type II (AEC-II) are able to generate IL-18 in primary culture. IL-18 was determined using semiquantitative reverse-transcription-PCR and localized in lungs using in situ hybridization. IL-18 protein levels were determined using the enzyme-linked immunosorbent assay and western blot analysis. Alveolar epithelial cells type II (AEC-II) were stimulated in vitro by proinflammatory cytokines, lipopolysaccharides, and whole cell lysate from Mycobacterium tuberculosis. IL-18 mRNA expression was significantly increased in the lungs affected by tuberculosis and sarcoidosis. In situ hybridization revealed different sites of expression in tuberculosis and sarcoidosis lungs, with AEC-II as one major source of IL-18 in the alveolar compartment. Basal IL-18 expression could be detected in normal AEC-II. Whole cell lysate from M. tuberculosis, but not lipopolysaccharide, led to a strong increase of IL-18 mRNA accumulation in AEC-II. Resting AEC-II secreted only small amounts of IL-18, but intracellular IL-18 protein levels increased in a time-dependent manner during culture. Proinflammatory cytokines tumour necrosis factor-alpha, IL-1beta, and interferon-gamma altered IL-18 mRNA expression and mature protein secretion of human AEC-II. These findings indicate a possible role for AEC-II and AEC-II-derived IL-18 in pathomechanisms of granulomatous lung diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / pharmacology
  • Epithelial Cells / chemistry
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Humans
  • Interleukin-18 / analysis
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Mycobacterium tuberculosis / immunology*
  • Protein Transport
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / immunology*
  • Pulmonary Alveoli / microbiology*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Sarcoidosis, Pulmonary / genetics
  • Sarcoidosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / genetics
  • Tuberculosis, Pulmonary / immunology*


  • Cytokines
  • Interleukin-18
  • Lipopolysaccharides
  • RNA, Messenger