To study the pathogenesis of multicentric Castleman's 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).

Cancers associated with marked neutrophilia are relatively rare. We report here two cases of anaplastic thyroid carcinoma associated with neutrophilia. We measured the concentrations of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in sera, pleural effusion, cyst fluid of the thyroid carcinoma region, or culture supernatants of carcinoma cells. Maximum levels of elevated white blood cell counts reached 106.1 x 10(9)/L (neutrophils 103.0 x 10(9)/L) in case 1 and 62.3 x 10(9)/L (neutrophils 57.9 x 10(9)/L) in case 2. Acute-phase reactants were elevated to various degrees, and hypercalcemia was found in both cases. IL-6, G-CSF, and M-CSF seemed to play the principal roles in neutrophilia in case 1, and the elevated levels of IL-6 and M-CSF seemed to mainly contribute to neutrophilia in case 2. Immunohistochemical staining revealed that carcinoma cells themselves produce IL-6 regardless of the types of carcinoma cells. To our knowledge, this is the first report describing the contribution of M-CSF to neutrophilia in patients with thyroid carcinoma.

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SUMMARYWe report here that T cells from patients with multicentric Castleman's disease (MCD) are sensitive to hyperthermia. T cells from two of three patients with MCD revealed DNA ladder formation and chromatin condensation following heat shock (30 min at 41 . 58C). Peripheral blood mononuclear cells (PBMC) from the same MCD patients exhibited high levels of spontaneous apoptosis after 72 h in culture and elevated apoptosis after heat shock, as evaluated by a quantitative flow cytometric assay. Heat shock protein 70 (hsp70) was detected on the cell surface of T cells in all three patients after heat shock. Furthermore, hsp70 was detected on T cells in the two MCD patients with apoptosis even in the absence of heat shock. T cells from normal samples did not show either heat-shock-induced expression of cell-surface hsp70 or apoptosis. Thus, heat shock treatment augmented hsp70 expression on the cell surface of T cells and enhanced apoptosis. Our studies suggest that hyperthermia may influence the clinical course of MCD.