Serum transforming growth factor-beta 1 is related to the degree of immunoparesis in patients with multiple myeloma

The expansion of myeloma cells is regulated by cytokines, among which IL-6 is a major growth factor. It has been recently suggested that serum transfo rming growth factor beta 1 (TGF beta 1), a cytokine found in large amounts in a-granules of platelets, might play a role in multiple myeloma (MM). It was the purpose of this study to determine serum TGF beta 1 levels in MM pa tients and to seek a correlation with disease parameters. Measurements were done by ELISA. We studied 35 MM patients (19 stage II, 16 stage III, 20 Ig G, 8 IgA and 6 BJ, 1 IgD) in different phases of the disease, 27 healthy in dividuals and 17 thrombocytopenic patients with other haematological diseas es (three MDS, three congenital thrombocytopenia, 11ITP). Overall samples f rom MM patients were included: 10 at diagnosis, 18 in remission and 32 in r elapse. In normal controls TGF beta 1 serum levels ranged from 1 to 33 ng/m l (median 16.5 ng/ml). In both thrombocytopenic controls with other disease s and thrombocytopenic MM patients (seven samples), TGF beta 1 serum levels were very low (median 3.2 and 4.5 ng/ml respectively). In MM patients with PLT > 100 x 10(9)/L (53 samples), TFG beta 1 serum levels were in the norm al range in patients without immunoparesis (1 to 27 ng/ml, median 16.6 ng/m l), whereas they were higher in patients with immunoparesis (polyclonal imm unoglobulins (Igs) below lower normal reference values) ranging from 10.2 t o 45 ng/ml (median 26.8 ng/ml) (P < 0.01). Serum TGF beta 1 levels fluctuat ed in the same patient at different times but not according to relapse or r emission. Correlation was found only between serum TGF beta 1 levels and im munoparesis and not between serum TGF beta 1 levels and disease stage or Ig subtype nor with prognostic factors for MM (serum CRP, beta 2M or IL-6). T his finding suggests that the remaining normal plasma cells are sensitive t o the inhibitory action of TGF beta 1 on Ig production. In conclusion TGF b eta 1 serum levels are very low in thrombocytopenic patients confirming tha t platelets are the major source of this cytokine. Furthermore, a strong co rrelation was found between TGF beta 1 serum levels and immunoparesis in MM patients.