Dysregulated peripheral and mucosal Th1/Th2 response in Whipple's disease.
OBJECTIVE
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.
Marth
Thomas
T
Internal Medicine II, University of the Saarland, Homburg/Saar, Germany. marth.gastro2@dkd-wiesbaden.de
Kleen
Nicole
N
Stallmach
Andreas
A
Ring
Sabine
S
Aziz
Sheriff
S
Schmidt
Carsten
C
Strober
Warren
W
Zeitz
Martin
M
Schneider
Thomas
T
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007107:Immune System / Q000503:physiopathology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D008061:Whipple Disease / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D016207:Cytokines; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma