Len also promotes CD4-cell secretion of IL-2 [14]

Len also promotes CD4-cell secretion of IL-2 [14]. 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. efficacy in the treatment of multiple myeloma (MM), and this prompted a large phase II study. Rabbit polyclonal to MCAM The primary end-point of this trial was paraprotein response. A response of 25% reduction in paraprotein was recorded in 27 patients (32%), and reductions of 90% of paraprotein CSRM617 Hydrochloride in serum and urine were documented in 8 patients. Using len/dexamethasone (dex) as initial therapy for myeloma, a decrease in serum monoclonal protein by 50% or greater was reported in 31 of 34 patients [4]. These findings suggest that the drugs may affect the synthesis of myeloma protein. Long before its use in MM, thal was known to be an effective treatment for erythema nodosum leprosum (ENL). This inflammatory condition occurs in multibacillary leprosy patients, and is thought to be, in part, an immune complex-mediated Type III hypersensivity [5,6]. Today, in addition to treating ENL and MM, thal is used to treat Waldenstr?ms macroglobulinemia, cutaneous lesions CSRM617 Hydrochloride of systemic lupus erythematosus, Schnitzlers syndrome, and light chain (AL) amylodosis. A common finding in these medical conditions is the detection of immunoglobulin in the skin lesions, or high levels of immunoglobulin or myeloma protein in serum and urine. Suppression of antibody synthesis by thal or len may offer an explanation for their effective treatment of MM and other conditions where over-production of immunoglobulin or light chains of immunoglobulin is involved. Pokeweed (PWM) promotes polyclonal differentiation of B cells into antibody-secreting cells, and it has been used to determine the effect of drugs on antibody synthesis [7]. We used this bioassay to see if thal, len or CSRM617 Hydrochloride dex could affect the synthesis of IgM, IgG, IL-2 and IL-6. 2. Materials and methods 2.1. Thalidomide, lenalidomide, dexamethasone Thal and len were synthesized to greater than 99% purity in the laboratory of NG. Len is an analog of thal, in which the phthalimide moiety is modified by removing oxygen on the number 3 carbon and adding an amino (NH2) group at the number 4 carbon (Fig. 1). They were dissolved in dimethyl sulfoxide (DMSO) and diluted in RPMI-1640. The final concentration of DMSO in the cultures was 0.08% volume/volume. Dex (Sigma, MO) was dissolved in pyrogen-free distilled water, and diluted in RPMI-1640. Open in a separate CSRM617 Hydrochloride window Fig. 1 Structure of thalidomide and lenalidomide. 2.2. Cell culture Blood was collected from donors at the Blood Bank of Our Lady of the Lake Hospital, and the Medical Oncology Clinic in Baton Rouge, Louisiana. The peripheral blood mononuclear cells (PBMC) were isolated and suspended in RPMI-1640 supplemented with 2 mM glutamine, Hepes, and 20% FCS. The PBMC at 1105 cells/well were incubated in: (1) a volume of 200 l; (2) with 5% CO2 in humidified air at 37 C; (3) and stimulated with PWM. The cultures were treated with len, thal or dex at 15 M each or len plus dex (len/dex). The supernatant was harvested after 6 days for assessment of immunoglobulin, IL-2 or IL-6. The cells were.