Comparative Analysis of Cytokines Released by Bone Marrow Stromal Cells from Normal Donors and B-cell Chronic Lymphocytic Leukemic Patients

Abstract

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)