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

Abstract

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.

• Authors: Thomas Marth, Nicole Kleen, Andreas Stallmach, Sabine Ring, Sheriff Aziz, Carsten Schmidt, Warren Strober, Martin Zeitz, Thomas Schneider
• Journal: Gastroenterology (Gastroenterology) Vol. 123 Issue 5 Pg. 1468-77 (Nov 2002) ISSN: 0016-5085 [Print] United States
• PMID: 12404221 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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, immunology, metabolism)