NATURAL-KILLER-STIMULATORY EFFECT OF COMBINED LOW-DOSE INTERLEUKIN-2 AND INTERFERON-BETA IN HAIRY-CELL LEUKEMIA PATIENTS

The association of low doses of interleukin-2 (IL-2; 5 IU/ml) and inte rferon P (IFN beta; 10 IU/ml) induced an additive or synergic stimulat ory effect on natural killer (NK) activity (32%) in peripheral blood s amples from hairy-cell leukemia patients, both those with active disea se and those in remission. The synergic NK stimulatory effect was more commonly found in samples from patients with active disease, while th e additive effect was more frequent in the patients in remission. The IL-2/IFN beta combination provoked a nonadditive nonsynergic NK-stimul atory effect in a further 19.8% samples. The targets of the IL-2/IFN b eta combination were typical NK cells, as shown by the fact that there was increased cytotoxicity (synergic, additive or nonadditive nonsyne rgic) against the K562, but not the Daudi cell line in peripheral bloo d mononuclear cell samples treated with the combination of the two cyt okines. When CD16(+)/CD56(+) or CD57(+)/CD16(+)/CD56(+) cells were rem oved, the NK-stimulatory effect was lost. The fact that the NK-cell-en hancing activity of the IL-2/IFN beta combination was reduced when Per coll fractions 2 and 3 were used, but still persisted in 66% of tests, may have been due to cytotoxicity being higher in the untreated fract ions 2 and 3 than in the untreated unfractionated samples. One of the factors responsible for the NK-stimulatory effect appears to be the ca pacity of the IL-2/IFN beta combination to trigger an increase in LFN gamma synthesis. If similar experiments give like results in samples f rom patients suffering from other B-cell lymphoproliferative, or HTV-a ssociated disorders, all of which are characterized by a deficiency in NK activity, it should be possible to use low-dose IL-2/IFN beta to t reat these disorders and, perhaps, residual neoplastic disease without exposing the patient to undue toxicity. Further, by testing other com binations one should be able to identify the lowest IL-2 and IFN beta doses that would effectively boost the additive or synergic effect in a greater number of cases.