In vivo interleukin 6 gene expression in the tumoral environment in multiple myeloma.
Whether interleukin 6 (IL 6) is an autocrine or paracrine myeloma cell growth factor in vivo remains unresolved. To identify which cells are producing IL 6 in vivo, we have studied the IL 6 gene expression in bone marrow mononuclear cells (BMMC) of 19 patients with multiple myeloma (MM) and in peripheral blood mononuclear cells (PBMC) of 9 patients with plasma cell leukemia (PCL). We found that the IL 6 gene was transcribed by BMMC of most patients with MM (79%). Further, IL 6 mRNA was not produced by purified myeloma cells from patients with either MM (5 patients) or PCL, but by the bone marrow environment, mainly by monocytes and myeloid cells (CD13+CD15+ cells). For 2 patients with PCL, for whom PBMC and BMMC samples were available, IL 6 mRNA could be detected in BMMC but not in PBMC. Finally, no IL 6 mRNA was detected in five freshly established IL 6-dependent myeloma cell lines. The present data give a clear-cut demonstration of the paracrine origin of IL 6 in vivo in human MM.
Portier
M
M
Immunopathologie Affections Tumorales et Autoimmunes, Montpellier, France.
Rajzbaum
G
G
Zhang
X G
XG
Attal
M
M
Rusalen
C
C
Wijdenes
J
J
Mannoni
P
P
Maraninchi
D
D
Piechaczyk
M
M
Bataille
R
R
D001853:Bone Marrow / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D007952:Leukemia, Plasma Cell / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D012333:RNA, Messenger