title: Lenalidomide alone or lenalidomide plus dexamethasone significantly inhibit IgG and IgM in vitro... A possible explanation for their mechanism of action in treating multiple myeloma.
abstract: Lenalidomide (len) is an analog of thalidomide (thal), and both are used in the treatment of a diverse group of medical conditions. A common finding in this group is the detection of immunoglobulin in skin lesions, or high levels of immunoglobulin or myeloma protein in serum and urine. While their mechanism(s) of action is not known, the drugs are noted for their ability to modulate monocyte, lymphocyte, and natural killer cell functions; suppression of immunoglobulin synthesis could offer an explanation for their effectiveness in treating multiple myeloma (MM). Our objective was to determine if, on an equimolar basis, thal, len or dexamethasone (dex) could affect pokeweed (PWM)-induced synthesis of IgG, IgM and IL-2. When peripheral blood mononuclear cells were stimulated with PWM, len surpassed thal in suppressing IgM and IgG, and enhancing IL-2. Dex enhanced IgG, and suppressed IL-2. When the stimulated cells were treated with len (an effective promoter of IL-2 and suppressor of IgM and IgG) plus dex (an effective suppressor of IL-2 and enhancer of IgG), the net result was suppression of IgM and IgG. The synthesis of IgM and IgG by putative PWM-stimulated B cell blasts is significantly blocked by len. This suggest that the B-lymphocyte is a targeted cell for len, and that suppression of the synthesis of IgG and IgM could provide an explanation for the mechanism by which len effectively treats MM.
authors.affiliation: U.S. Department of Health and Human Services, Health Resources and Services Administration, National Hansen's Disease Programs, Lab Research Branch at Louisiana State University, Baton Rouge, LA 70803, USA. eshannon@hrsa.gov
authors.forename: E
authors.initials: E
authors.lastname: Shannon
authors.forename: F
authors.initials: F
authors.lastname: Sandoval
authors.forename: N
authors.initials: N
authors.lastname: Greig
authors.forename: P
authors.initials: P
authors.lastname: Stagg
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D000077269:Lenalidomide; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology; D011043:Pokeweed Mitogens / Q000276:immunology / Q000494:pharmacology; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D015850:Interleukin-6; D011043:Pokeweed Mitogens; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide