Akimoto Y

Immunodeficiency and IL‐6 production by peripheral blood monocytes in multicentric Castleman's disease

Summary. To study the pathogenesis of multicentric Castlemans disease (MCD), IL‐6 producing cells and immune function were investigated in four MCD patients. The expression of IL‐6 mRNA in one MCD lymph node was analysed by in situ hybridization. IL‐6 mRNA expressing cells were scattered in the interfollicular areas and did not resemble plasma cells. Spontaneous IL‐6 production was detected in the culture supernatants of peripheral blood mononuclear cells (PBMNC) from four patients. The IL‐6 producing cells among the PBMNC were found to be monocytes by both in situ hybridization and immunohistochemistry. We evaluated immune function in four MCD patients. These studies show: (1) a negative PPD skin test in 3/4 patients. (2) decreased IL‐2 production in 3/4 patients, (3) decreased T cell colony formation in 3/4 patients, (4) decreased NK activity and NK cell number in 2/4 patients, (5) increased soluble IL‐2 receptor in 4/4 patients, and (6) decreased CD4/CD8 ratio in 3/4 patients. These results show that MCD resembles, in several ways, acquired immunodeficiency syndrome (AIDS).

Interleukin-6 receptor expression in the peripheral B cells of patients with multicentric Castleman's disease

Abstract Interleukin-6 (IL-6) is an important regulator of terminal B-cell differentiation. Inappropriate oversynthesis of IL-6 may play a primary role in the pathogenesis of multicentric Castlemans disease (MCD). We investigated the expression of the IL-6 receptor (IL-6R) in peripheral B cells from three patients with MCD, as well as the responsiveness of these cells to IL-6. Flow-cytometric analysis showed that IL-6R was significantly expressed on the peripheral B cells of two of three patients. The B cells expressing IL-6R spontaneously produced increased levels of immunoglobulin G (IgG). IL-6R-expressing B cells from one patient showed hyper-responsiveness to IL-6.

The presence of CD28-negative T cells in a patient with multicentric Castleman's disease

Abstract We found increased numbers of CD28-negative T cells in a patient with multicentric Castlemans disease (MCD), who also had significantly decreased interleukin-2 (IL-2) production and impaired T-cell proliferation. The presence of CD28-negative T cells may be indicative of a functional T-cell defect in MCD.

Spontaneous IL-2 production in vitro in two patients with pure red cell aplasia

SummaryWe investigated spontaneous cytokine production in two patients with pure red cell aplasia (PRCA). The peripheral blood mononuclear cells (PBMNC) from two patients produced IL-2. Cyclosporin A (CyA) suppressed in vitro IL-2 production in one patient, but not in the other. Spontaneous IL-2 production disappeared in one patient 10 months after the start of CyA therapy. The patient for whom CyA therapy was stopped after the disappearance of spontaneous IL-2 production has remained in continuous remission for 1 year. The present case suggests that spontaneous IL-2 production in PBMNC might be an indicator of disease activity.