Modulation of Proinflammatory Cytokines and Insulinlike Growth Factor-1 (IGF-1) in Human Immunodeficiency Virus-1 Smoldering Multiple Myeloma (HIVSMM) Patients

Abstract 5043

Multiple myeloma is a B-cell malignancy involving germinal center B cells characterized by blood and urinary monoclonal proteins, osteolytic bone lesions and infiltration of bone marrow with plasma cells wit pathology involving aberrant chromosomal translocation with increased glucose uptake (Warburg Phenomena). This glucose transporter (GLUT) is activated and over expressed along with proinflammatory cytokines produced by malignant plasma cells both smoldering and multiple myeloma (MM). These cytokines may control growth, progression and dissemination. Interleukin-6 (IL-6) is a major cytokinetic growth factor in MM but IGF-1 is a more prominent growth factor that binds to IGF-1 receptor (IGF-1R) and is a strong indicator of prognosis which can augment anti-apoptotic effects of IL-6. Modulation of IGF-1 and proinflammatory cytokines in HIVSMM patients with ritonavir-based highly active antiretroviral therapy (RTV-based HAART) may suppress nuclear factor kappa b (NF Kb) and inhibit the overexpression of GLUT-1–4 required for HIVSMM growth and viability. A selenium adjuvant RTV-based HAART abrogates GLUT activity with specificity for GLUT-4 (prominent growth factor in MM cells. We present a 44 YOF with an with HIV disease, anemia, CD4 cell count of 74/cumm, viral load > 1 million copies/ml, SMM with IgG kappa/lambda 3. 68 grams/L, a hypocellular bone marrow biopsy with > 60 % plasma cell (polytypic) and with an increase in immature forms. Her serum free light chains (SFLC) on diagnosis was 324 mg/dl/121 mg/dl kappa/lambda ratio of 2. 68, bone scan with no evidence of lytic lesions and beta-2-microglobulin (B2MG) of 14. 40 mg/L: soluble interleukin-2 receptor (sIL2R) of 10, 833. 47 pg/ml; IGF-1 was 346 ng/ml (Nl = 94–250 ng/ml); selenium level was 137 mg/dl; C-reactive protein (CRP) of 38 mg/dl. After three years of selenium-RTV-based-HAART therapy her proinflammatory markers trended downward. CD4 cell count now is 348/cumm; viral load of 25. 7 copies/ml; SMM IgG 0. 972 grams/L; SFLC of 35. 9mg/dl/35mg/dl kappa/lambda ratio of 1. 03; B2MG of 2. 24 mg/L; sIL2R of 6546. 14 pg/ml; IGF-1 of 128 ng/ml; selenium of 150mg/dl; and CRP of 0. 26 mg/dl.