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 with IL-2 on MDS bone marrow and peripheral blood cells. Thirty-six patients 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), which then were resuspended in medium containing IL-2, IL-12 or IL-2 + IL-12 for 7 days. Re-evaluation of NK-a levels, lymphocyte immunophenotypes, clonogenic activity and cytokine release showed that, unlike IL-2, IL-12 did not significantly increase NK-a or CD3-/56+ cell levels in either bone marrow or peripheral blood; IL-2 + 12 led to a significant increase that fell between the values reached by each cytokine alone. IL-2 + 12 and, although to a lesser extent, also IL-12 alone induced the release of large amounts of gamma-IFN and alpha-TNF. In addition, the number of clusters particularly decreased in the samples treated with IL-2 + 12 and IL-12 alone. Clonogenic activity was not modified after stimulation with any of the treatment. These data suggest that 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.
Sarina
B
B
Servizio di Ematologia, Università di Milano, IRCCS Ospedale Maggiore, Italy.
Cortelezzi
A
A
Cattaneo
C
C
Pomati
M
M
Silvestris
I
I
Di Stefano
M
M
Lambertenghi-Deliliers
D
D
Hu
C
C
Monza
M
M
Maiolo
A T
AT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D010641:Phenotype
D016207:Cytokines; D007376:Interleukin-2; D018664:Interleukin-12