IN-VITRO EFFECTS OF IL-12 AND IL-2 ON NK CELLS, CYTOKINE RELEASE AND CLONOGENIC ACTIVITY IN MYELODYSPLASTIC SYNDROMES (MDS)

We evaluated the in vitro effects of IL-12, alone and in association w ith IL-2 on RIDS bone marrow and peripheral blood cells. Thirty-six pa tients and 14 healthy subjects were studied. Natural killer-activity ( NK-a) levels and lymphocyte immunophenotypes were determined in fresh bone marrow (BMMNC) and peripheral blood mononuclear cells (PBMNC), wh ich then were resuspended in medium containing IL-2, IL-12 or IL-2 + I L-12 for 7 days. Re-evaluation of NK-a levels, lymphocyte immunophenot ypes, clonogenic activity and cytokine release showed that, unlike IL- 2, IL-12 did not significantly increase NK-a or CD3(-)/56(+) cell leve ls in either bone marrow or peripheral blood; IL-2 + 12 led to a signi ficant increase that fell between the values reached by each cytokine alone. IL-2 + 12 and, although to a lesser extent, also IL-12 alone in duced the release of large amounts of gamma-IFN and alpha-TNF. In addi tion, the number of clusters particularly decreased in the samples tre ated with IL-2 + 12 and IL-12 alone. Clonogenic activity was not modif ied after stimulation with any of the treatment. These data suggest th at IL-12 induces the release of inhibitory cytokines in normal as well as MDS cells and that it could be used in patients with elevated bone marrow blastosis.