CYTOKINES RELEASED IN-VITRO BY STROMAL CELLS FROM AUTOLOGOUS BONE-MARROW TRANSPLANT PATIENTS WITH LYMPHOID MALIGNANCY

Marrow stromal cells of patients treated by autologous bone marrow tra nsplantation (ABMT) for malignancies have been assessed for their abil ity to secrete granulocyte colony-stimulating factor (G-CSF), granuloc yte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (S CF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), transform ing growth factor beta 1 (TGF beta 1) and macrophage inflammatory prot ein-1 alpha (MIP-1 alpha). Long-term marrow cultures were established from 10 patients prior to and 3 months after ABMT, from 7 patients 1 y r after ABMT and from 11 controls. Cytokines in culture supernatants o f stromal layers (SL) were evaluated by enzyme-linked immunosorbent as say (ELISA). Significant differences between patient groups and contro ls were apparent in baseline production of GM-CSF, SCF, MIP-1 alpha an d TGF beta 1. After IL-1 beta addition in cultures, G-CSF production w as reduced in pretransplant and post-transplant patients compared to c ontrols. The production of TGF beta 1, LIF, IL-6 and more particularly SCF were reduced in post-transplant patients, while elevated levels o f GM-CSF and MIP-la were observed in these patients only when the valu es were corrected for the number of cells growing in the SL. These res ults indicate a prolonged stromal defect in growth factor production f ollowing ABMT for the early-stage acting cytokines IL-6, LIF and SCF a s well as for G-CSF, but not for GM-CSF, while the production of the 2 inhibitors shows different pathways.