Defects of monocyte interleukin 12 production and humoral immunity in Whipple's disease

Abstract

Background and Aims: 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 α, interferon gamma (IFN- γ), and transforming growth factor β (TGF-β) 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-γ secretion by peripheral blood mononuclear cells in vitro were found, as well as reduced immunohistological staining for IL-12 and IFN-γ, 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-γ-dependent Ig subclass, and serum TGF-β levels were reduced in patients with WD. Conclusions: The described monocyte defects in WD may result in a secondary reduction of IFN-γ production and IgG2 serum levels. This provides a rationale for additive immunotherapy in patients with antibiotic-refractory WD.