Castleman's Disease and Interleukin 6

Castleman's disease is a rare condition characterized by benign hyperplastic lymph nodes. Based on the morphological features, it has been divided into hyaline-vascular, plasma cell and intermediate types. The latter two types are frequently associated with a wide variety of clinical pictures such as fever, anemia with hypotransferrinemia, hyperimmunoglobulinemia and an increase in the concentration of C-reactive protein (CRP). Although immunological disturbances have been suggested to play important roles in the pathophysiology of Castleman's disease, the precise mechanisms for the generation of its clinical pictures are still unsettled. In this respect, we have reported a pediatric case with spontaneous production of high levels of B cell differentiation factor (BCDF) activity by the hyperplastic lymph node, and we demonstrated here the strong expression of interleukin 6 (IL-6) gene in the lymph node cells. On the other hand, recent studies have revealed that IL-6 is a multifunctional cytokine; IL-6 not only induces the immunoglobulin production but also induces the acute phase reaction, and functions as an endogeneous pyrogen. In the acute phase reaction, IL-6 may induce an increase in CRP concentration and hypotransferrinemia. These studies indicate that the overproduction of IL-6 by the hyperplastic lymph node may be closely related to the pathophysiology of Castleman's disease. Therefore, it is considered that this disease is a "disorder of IL-6 production".