No abstract

Castleman's disease is a syndrome consisting of giant lymph node hyperplasia with plasma cell infiltration, fever, anemia, hypergammaglobulinemia, and an increase in the plasma level of acute phase proteins. It has been reported that clinical abnormalities disappear after the resection of the affected lymph nodes, suggesting that products of lymph nodes may cause such clinical abnormalities. Interleukin-6 (IL-6) is a cytokine inducing B-cell differentiation to immunoglobulin-producing cells and regulating biosynthesis of acute phase proteins. This report demonstrates that the germinal centers of hyperplastic lymph nodes of patients with Castleman's disease produce large quantities of IL-6 without any significant production of other cytokines. In a patient with a solitary hyperplastic lymph node, clinical improvement and decrease in serum IL-6 were observed following surgical removal of the involved lymph node. There was a correlation between serum IL-6 level, lymph node hyperplasia, hypergammaglobulinemia, increased level of acute phase proteins, and clinical abnormalities. The findings in this report indicate that the generation of IL-6 by B cells in germinal centers of hyperplastic lymph nodes of Castleman's disease may be the key element responsible for the variety of clinical symptoms in this disease.

Castleman's disease is a syndrome consisting of giant lymph node hyperplasia with plasma cell infiltration, fever, anemia, hypergammaglobulinemia, and an increase in the plasma level of acute phase proteins. It has been reported that clinical abnormalities disappear after the resection of the affected lymph nodes, suggesting that products of lymph nodes may cause such clinical abnormalities. Interleukin-6 (IL-6) is a cytokine inducing B-cell differentiation to immunoglobulin-producing cells and regulating biosynthesis of acute phase proteins. This report demonstrates that the germinal centers of hyperplastic lymph nodes of patients with Castleman's disease produce large quantities of IL-6 without any significant production of other cytokines. In a patient with a solitary hyperplastic lymph node, clinical improvement and decrease in serum IL-6 were observed following surgical removal of the involved lymph node. There was a correlation between serum IL-6 level, lymph node hyperplasia, hypergammaglobulinemia, increased level of acute phase proteins, and clinical abnormalities. The findings in this report indicate that the generation of IL-6 by B cells in germinal centers of hyperplastic lymph nodes of Castleman's disease may be the key element responsible for the variety of clinical symptoms in this disease.

No abstract

Accidental inoculation of a root extract of Phytolacca americana (pokeweed) was noted in 1965 to induce a wave of lymphoblasts and plasma cells in the circulation (1), and mitogenic extracts from this plant have proven very useful for the in vitro study of human B cell differentiation (2). The responsive B cells in blood are slowly acquired during infancy (3), require non-major histocompatibility complex-(MHC) restricted T cell helper factors for activation (2, 4), express surface IgM more often than IgG and IgA, and are easily and selectively inhibited by antibodies to these immunoglobulin (Ig) isotypes (5). In contrast, anti-8 antisera have been reported to have variable effects on pokeweed mitogen (PWM)-induced differentiation of B cells (6, 7). Other studies have suggested that PWM-responsive cells are of relatively low buoyant density (8) and lack the receptors for mouse erythrocytes found on many human B cells (9).In the present studies, we examined the expression of IgD on PWM-responsive B cells and correlated these features with cell density, size, and capacity to bind mouse erythrocytes. The results suggest that this is a distinct subpopulation of B cells that are preactivated in vivo. Materials and MethodsCell Preparation and Culture. Human mononuclear cells (MNC) obtained from heparinized venous blood of healthy donors by Ficoll-Hypaque gradient centrifugation were incubated at 37°C for 1 h in a plastic dish. Nonadherent cells were adjusted to the concentration of 1 × 10 ° cells/ml in RPMI 1640 supplemented with 10% heat-inactivated fetal calf serum (FCS) (Gibco Laboratories, Grand Island Biological Co., Grand Island, NY) 2 mM L-glutamine, 50 #g/ml gentamicin, and 5 × 10 -s M 2-mercaptoethanol. Cultures were established in flat-bottomed microplates (Costar, Data Packaging, Cambridge, MA) with each well containing 0.2 ml of the cell suspension and an optimum concentration of pokeweed mitogen (5/zl/ml of PWM; Gibco) and held at 37°C for 7 d in a humid atmosphere of 5% CO2 and 95% air.Monoclonal Anti-~ Antibody. This mouse monoclonal hybridoma antibody (8-TA4-1, T3x) was prepared by