Interferon-gamma in multiple myeloma.

Biological heterogeneity is a characteristic of multiple myeloma. A dysregulated cytokine network underlies the various phases of the disease. Numerous cytokines, either promoting or inhibiting plasma cell growth, are involved in tumor control. Interferon-gamma (IFN-gamma) showed the most powerful inhibiting activity on myeloma cell proliferation. This effect was demonstrated on IL-6 dependent myeloma cell lines, but not on IL-6 independent ones. It was also evident on fresh explanted bone marrow myeloma cells. The antiproliferative effect of IFN-gamma seems mainly due to the inhibition of IL-6, the central myeloma growth factor. IL-6 inhibition may occur at various levels: a downregulation of IL-6 receptor has been reported, and also a block of the IL-6 signal transduction pathway via interaction with cytoplasmic proteins such as p91 has been suggested. Our findings showed that IFN-gamma strongly inhibited myeloma cell proliferation to the same extent as dexamethasone (DEX), whereas interferon-alpha (IFN-alpha) inhibited Ig secretion. The combined use of interferons (IFNs) showed inhibitory activities both on proliferation and Ig synthesis that paralleled the effects of DEX. In some cases, IFN-gamma was also shown to augment monoclonal immunoglobulin secretion suggesting a possible differentiating activity on plasma cells. The in vitro data encouraged pilot studies to evaluate the in vivo antitumor effects of IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)