TY - JOUR
T1 - Effects of IL-6 variants in multiple myeloma
T2 - Growth inhibition and induction of apoptosis in primary cells
AU - Petrucci, Maria Teresa
AU - Ricciardi, Maria Rosaria
AU - Gregorj, Chiara
AU - Ciapponi, Laura
AU - Savino, Rocco
AU - Ciliberto, Gennaro
AU - Tafuri, Agostino
PY - 2002/12/1
Y1 - 2002/12/1
N2 - Interleukin-6 (IL-6) plays a pathogenetic role in B-cell malignancies and is a growth factor for multiple myeloma (MM) cells. Elevated serum IL-6 levels and a higher proliferative activity of bone marrow plasma cells are poor prognostic factors in MM patients. In addition to clinical trials with anti-IL-6 monoclonal antibodies, an alternative therapeutic approach based on the use of IL-6 receptor (R) super-antagonists (Sants) has been proposed. Sants are variants of the native cytokine characterized by a wild type affinity for the ligand-specific receptor chain IL-6R alpha and by a reduced ability to bind and/or dimerize the signaling chain gp-130. We report the in vitro effects of four different Sants on cell kinetic modulation and induction of apoptosis of primary cells from MM patients. Ten MM samples were cultured in the presence of four different Sants and heterogeneous effects in terms of reduction of proliferation and induction of apoptosis could be observed. A decrease of the S phase cells (≥ 25%) coupled with the induction of apoptosis was obtained in 4/10 samples: three of these samples had a diploid DNA stem line and an inferior initial percentage of S phase cells. Serum IL-6 concentrations did not correlate with the anti-proliferative activities of the Sants. Cell growth inhibition was observed especially in samples with soluble IL-6R serum concentrations > 200 ng/ml. We conclude that Sants can exert antiproliferative effects on selected MM samples. Such effects may depend on the availability of large amounts of soluble IL-6R. Further studies should aim at defining the conditions necessary for optimal antiproliferative activity.
AB - Interleukin-6 (IL-6) plays a pathogenetic role in B-cell malignancies and is a growth factor for multiple myeloma (MM) cells. Elevated serum IL-6 levels and a higher proliferative activity of bone marrow plasma cells are poor prognostic factors in MM patients. In addition to clinical trials with anti-IL-6 monoclonal antibodies, an alternative therapeutic approach based on the use of IL-6 receptor (R) super-antagonists (Sants) has been proposed. Sants are variants of the native cytokine characterized by a wild type affinity for the ligand-specific receptor chain IL-6R alpha and by a reduced ability to bind and/or dimerize the signaling chain gp-130. We report the in vitro effects of four different Sants on cell kinetic modulation and induction of apoptosis of primary cells from MM patients. Ten MM samples were cultured in the presence of four different Sants and heterogeneous effects in terms of reduction of proliferation and induction of apoptosis could be observed. A decrease of the S phase cells (≥ 25%) coupled with the induction of apoptosis was obtained in 4/10 samples: three of these samples had a diploid DNA stem line and an inferior initial percentage of S phase cells. Serum IL-6 concentrations did not correlate with the anti-proliferative activities of the Sants. Cell growth inhibition was observed especially in samples with soluble IL-6R serum concentrations > 200 ng/ml. We conclude that Sants can exert antiproliferative effects on selected MM samples. Such effects may depend on the availability of large amounts of soluble IL-6R. Further studies should aim at defining the conditions necessary for optimal antiproliferative activity.
KW - Apoptosis
KW - Cell cycle
KW - IL-6
KW - IL-6 receptor-superantagonists
KW - Multiple myeloma
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U2 - 10.1080/1042819021000040224
DO - 10.1080/1042819021000040224
M3 - Article
C2 - 12613526
AN - SCOPUS:0036892050
VL - 43
SP - 2369
EP - 2375
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
SN - 1042-8194
IS - 12
ER -