Treatment of renal failure associated with multiple myeloma and other diseases by PACAP-38.

Myeloma kidney injury is caused by the large amount of light chain (LC) of immunoglobulins produced by cancerous plasma cells through stimulation of proinflamatory cytokines like TNF-alpha and IL-6. PACAP-38 suppressed LC-stimulated cytokine production by tubular epithelial cells in vitro and in vivo, and prevented injury of these epithelial cells. The suppressive effect is comparable or greater than dexamethasone (dex). Although dex produces adverse side effects when it is given for a long time period, PACAP-38 is a natural and safe neuropeptide and no adverse effect has been reported when administered to produce significant biological effects. Furthermore, PACAP-38 suppressed growth of myeloma cells in culture and also suppressed production of their growth factor, IL-6, production from the bone marrow stromal cells that was stimulated by adhesion of myeloma cells. These findings render PACAP-38 worth evaluation as a safe and potent renoprotectant in myeloma kidney as well as a new antitumor agent for myeloma cells.