Defects of monocyte interleukin 12 production and humoral immunity in Whipple's disease.
OBJECTIVE
Whipple's disease (WD) is a systemic infection in which the causative bacteria typically accumulate within macrophages. The aim of this study was to test whether this macrophage dysfunction is the cause or result of previously shown T-cell defects.


METHODS
In vitro production of interleukin (IL)-12, IL-10, tumor necrosis factor alpha, interferon gamma (IFN-gamma), and transforming growth factor beta (TGF-beta) from purified monocytes and peripheral blood mononuclear cells, cytokine expression on duodenal biopsy specimens, and serum cytokine and immunoglobulin (Ig) levels were tested in 9 patients with WD.


RESULTS
Reduced monocyte IL-12 production and decreased IFN-gamma secretion by peripheral blood mononuclear cells in vitro were found, as well as reduced immunohistological staining for IL-12 and IFN-gamma, but no decrease in other cytokines in patients with WD. A similar but less severe defect in 2 relatives with WD argued for a genetic basis of this abnormality. Serum IgG2, an IFN-gamma-dependent Ig subclass, and serum TGF-beta levels were reduced in patients with WD.


CONCLUSIONS
The described monocyte defects in WD may result in a secondary reduction of IFN-gamma production and IgG2 serum levels. This provides a rationale for additive immunotherapy in patients with antibiotic-refractory WD.
Marth
T
T
Mucosal Immunity Section, National Institutes of Health, Bethesda, Maryland, USA. Intmar@med-rz.uni-sb.de
Neurath
M
M
Cuccherini
B A
BA
Strober
W
W
D000917:Antibody Formation / Q000276:immunology; D002478:Cells, Cultured; D015925:Cryopreservation; D016207:Cytokines / Q000096:biosynthesis; D004386:Duodenum / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D008061:Whipple Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D007074:Immunoglobulin G; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma