Dysregulated peripheral and mucosal Th1/Th2 response in Whipple's disease

Gastroenterology. 2002 Nov;123(5):1468-77. doi: 10.1053/gast.2002.36583.


Background & aims: An impaired monocyte function and impaired interferon (IFN)-gamma production has been suggested as a possible pathogenetic factor in Whipple's disease (WD) and as a cause for the delayed elimination of Tropheryma whipplei in some patients.

Methods: We studied, in a series of 20 WD patients with various degrees of disease activity, cellular immune functions.

Results: We found an increased in vitro production of interleukin (IL)-4 by peripheral mononuclear blood cells as determined by enzyme-linked immunosorbent assay, but reduced secretion of IFN-gamma and IL-2 as compared with age- and sex-matched controls. In addition, we observed a significantly reduced monocyte IL-12 production in response to various stimuli in WD patients whereas other cytokines were comparable with controls; these immunologic alterations were not significantly different in patients with various disease activities. At the mucosal level, we found decreased CD4 T-cell percentage and a significantly impaired IFN-gamma secretion.

Conclusions: Our data define a defective cellular immune response in a large series of WD patients and point to an important pathogenetic role of impaired Th1 responses. The decreased monocyte IL-12 levels may result in reduced peripheral and mucosal IFN-gamma production and lead to an increased susceptibility to T. whipplei infection in certain hosts.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Female
  • Gastric Mucosa / metabolism*
  • Humans
  • Hypersensitivity, Delayed / etiology
  • Immune System / physiopathology
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Intestinal Mucosa / metabolism*
  • Male
  • Middle Aged
  • Th1 Cells / metabolism*
  • Th2 Cells / metabolism*
  • Whipple Disease / drug therapy
  • Whipple Disease / immunology
  • Whipple Disease / metabolism*


  • Anti-Bacterial Agents
  • Cytokines
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma