Defective Th1 responses and augmented IL-4 production in patients with Whipple's disease

Abstract

1440720 Background: An impaired monocyte interleukin-12 (IL-12) and T cell interferon-y (IFN-y) production has been suggested in several patients as possible pathogenetic factor in Whipple s disease (WD) and cause for the delayed elimination of the causative bacteria, Tropheryma whippelii. Methods and Results: In the present study we found in a series of 15 WD patients with various disease activity an increased in vitro production of IL-4 (31.5 ::':: 6.2 pglml for WD patients versus 19.7 ::':: 3.8 pg/ml for controls; p<0.05) by peripheral mononuclear blood cells (PBMC) but reduced secretion of IFN-y (476 ::':: 135 vs. 1307 ::':: 395 pglml; p<O.01) and IL-2 (175 ::':: 40 vs. 253 ::':: 78; p<0.05) as compared to age and sex matched healthy controls. T cell proliferation in response to lectins was reduced in all patient groups versus the controls. For cytokines of monocyte origin, we observed a significantly reduced IL-12 production in response to various stimuli in WD patients whereas other cytokines such as secretion of tumor necrosis factor a (TNF-cx) were comparable to controls. Data of mucosal (lamina propria) cytokine secretion in four patients with WD showed similar reduction of IL-12 and IFN-y. These immunological alterations were even present in WD patients without clinical or histological signs of disease activity. Conclusions: Our data demonstrate a persistent defective cellular immune response and an enhancement of IL-4 secretion in a large series of WD patients. This polarized Th l/Th2 cytokine pattern is likely to facilitate engagement and survival of the causative bacteria and presents a pathogenetic basis for immunomodulatory therapy in patients with refractory WD.