Comparative analysis of cytokines released by bone marrow stromal cells from normal donors and B-cell chronic lymphocytic leukemic patients.
We studied the production of cytokines (G-CSF, GM-CSF, IL-6, LIF and IL-10) by bone marrow stromal cells of five untreated patients with B-CLL, in Rai stage 0, I and II, and of 8 healthy subjects. The production of G-CSF, GM-CSF, LIF and IL-10 did not differ significantly between controls and B-CLL patients. However, the ability of stromal cells to release IL-6 in response to LPS was decreased in all patients: 36 +/- 5 ng/ml versus 123 +/- 47 ng/ml for normal controls (p < 0.004). Moreover, a soluble activity that inhibited hematopoietic colony formation was detected in B-CLL stromal cell conditioned media. Some potential inhibitors were envisaged and the results indicated an increased production of TGF-beta by B-CLL stromal cells compared to normal stromal cells (respectively 53 +/- 10 versus 15 +/- 4 ng/ml, p < 0.03). The reduced capacity of B-CLL stromal cells to produce IL-6 was associated with this excessive release of TGF-beta; indeed, addition of anti-TGF-beta neutralizing antibody to B-CLL stromal cells, before LPS stimulation, totally normalized the production of IL-6. TGF-beta and IL-6 were also measured in serum samples from normal subjects and B-CLL patients. No significant difference was seen in the production of total TGF-beta (bioactive and latent forms) between normal and B-CLL sera but the mean level of bioactive protein in B-CLL sera was increased in comparison with normal sera (1.74 +/- 0.44 versus 0.67 +/- 0.2 ng/ml, p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
Lagneaux
L
L
Service de Médecine Interne et Laboratoire d'Investigation Clinique Henri Tagnon, Institut J. Bordet, Brussels, Belgium.
Delforge
A
A
Bron
D
D
Bosmans
E
E
Stryckmans
P
P
D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008875:Middle Aged; D012016:Reference Values; D017154:Stromal Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D003470:Culture Media; D016207:Cytokines; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha