INTERLEUKIN-6 PRODUCTION IN B-CELL NEOPLASIAS AND CASTLEMANS DISEASE - EVIDENCE FOR AN ADDITIONAL PARACRINE LOOP

Functioning as a B-cell growth and differentiation factor, interleukin -6 (IL-6) may play an important role in the pathophysiology of B-cell tumors. The capacity for IL-6 secretion was evaluated in 58 patients w ith various B-cell leukemias/lymphomas and in four patients with Castl eman's disease (CMD). Cell populations from various sites including pe ripheral blood, bone marrow, lymph nodes, and osteolytic bone lesions were cultured and tested for spontaneous or IL-1 beta/ TNF alpha-induc ed IL-6 production in a sensitive bioassay. No significant IL-6 levels were released by the tumor cells in any of the B-cell leukemias or ly mphomas tested, including hairy cell leukemia (HCL) and B-cell chronic lymphocytic leukemia (B-CLL). In contrast, purified malignant plasma cells were found to secrete IL-6, strengthening the idea that an autoc rine pathway for growth regulation in multiple myeloma (MM) exists. Fo r the first time, in several patients with CMD, peripheral blood cells were shown to produce extremely high levels of IL-6, the pathogenetic significance of which remains to be elucidated. However, similar obse rvations were very occasionally made in MM patients. Therapy with cort icosteroids strongly inhibited this IL-6 production. These data provid e evidence for autocrine and possibly an additional paracrine regulato ry loop in plasma cell neoplasias and CMD.