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. 1994 Sep;38(5):323–331. doi: 10.1007/BF01525511

Natural-killer-stimulatory effect of combined low-dose interleukin-2 and interferon β in hairy-cell leukemia patients

Anna Marina Liberati 1,✉, Verena De Angelis 1, Marco Fizzotti 1, Monica Schippa 1, Michela Cecchini 1, Daniela Adiuto 1, Francesco Di Clemente 1, Lucia Palmisano 2, Elisabetta Micozzi 3, Massimo Zuccaccia 4, Saverio Cinieri 1
PMCID: PMC11041105  PMID: 7512888

Abstract

The association of low doses of interleukin-2 (IL-2; 5 IU/ml) and interferon β (IFNβ; 10 IU/ml) induced an additive or synergic stimulatory effect on natural killer (NK) activity (32%) in peripheral blood samples from hairy-cell leukemia patients, both those with active disease and those in remission. The synergic NK stimulatory effect was more commonly found in samples from patients with active disease, while the additive effect was more frequent in the patients in remission. The IL-2/IFNβ combination provoked a nonadditive nonsynergic NK-stimulatory effect in a further 19.8% samples. The targets of the IL-2/IFNβ combination were typical NK cells, as shown by the fact that there was increased cytotoxicity (synergic, additive or nonadditive nonsynergic) against the K562, but not the Daudi cell line in peripheral blood mononuclear cell samples treated with the combination of the two cytokines. When CD16+/CD56+ or CD57+/CD16+/CD56+ cells were removed, the NK-stimulatory effect was lost. The fact that the NK-cell-enhancing activity of the IL-2/IFNβ combination was reduced when Percoll fractions 2 and 3 were used, but still persisted in 66% of tests, may have been due to cytotoxicity being higher in the untreated fractions 2 and 3 than in the untreated unfractionated samples. One of the factors responsible for the NK-stimulatory effect appears to be the capacity of the IL-2/IFNβ combination to trigger an increase in IFNγ synthesis. If similar experiments give like results in samples from patients suffering from other B-cell lymphoproliferative, or HIV-associated disorders, all of which are characterized by a deficiency in NK activity, it should be possible to use low-dose IL-2/IFNβ to treat these disorders and, perhaps, residual neoplastic disease without exposing the patient to undue toxicity. Further, by testing other combinations one should be able to identify the lowest IL-2 and IFNβ doses that would effectively boost the additive or synergic effect in a greater number of cases.

Key words: IFNβ, IL-2, NK cell activity, Hairy-cell leukemia, IFNγ

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