title: Dysregulated peripheral and mucosal Th1/Th2 response in Whipple's disease.
abstract: 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.
authors.affiliation: Internal Medicine II, University of the Saarland, Homburg/Saar, Germany. marth.gastro2@dkd-wiesbaden.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Marth
authors.forename: Nicole
authors.initials: N
authors.lastname: Kleen
authors.forename: Andreas
authors.initials: A
authors.lastname: Stallmach
authors.forename: Sabine
authors.initials: S
authors.lastname: Ring
authors.forename: Sheriff
authors.initials: S
authors.lastname: Aziz
authors.forename: Carsten
authors.initials: C
authors.lastname: Schmidt
authors.forename: Warren
authors.initials: W
authors.lastname: Strober
authors.forename: Martin
authors.initials: M
authors.lastname: Zeitz
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma