INTERLEUKIN-2 TREATMENT-ASSOCIATED EOSINOPHILIA IS MEDIATED BY INTERLEUKIN-5 PRODUCTION

Summary During a trial using recombinant human interleukin‐2 (rhIL‐2) immunotherapy for acute myeloblastic leukaemia (AML) in remission, eosinophilia was observed in all patients. We used in‐vitro clonogenic assays to investigate the mechanism of the eosinophilia in five patients. The mean eosinophil count increased from 0.05 ± 109/1 before rhTL‐2 to 0.98 ± 109/1 within 48 h of stopping the infusion, and an exponential correlation between the pre‐treatment lymphocyte CD4:CD8 ratio and the maximum eosinophil count was observed. KhIL‐2 did not stimulate eosinophil colony formation by normal bone marrow. However, serum collected from patients during rhIL‐2 infusion was a potent stimulator of eosinophil colony forming units (CFU‐Eo), but had no significant stimulatory effect on granulocyte‐macrophage colony forming units (CFU‐GM). The CFU‐Eo stimulation by pre‐treatment serum was 2.8‐fold higher than control serum. Serum collected during treatment stimulated CFIJ‐Eo 12 times more than control serum (P<045). By pre‐incubating patient serum, collected during rhIL‐2 treatment, with monoclonal antibodies to murine IL‐5. or human granulocyte‐macrophage colony stimulating factor (GM‐CSF). a reduction of 80% and 38% respectively in eosinophil and GM colony production was found. The CFU‐Eo stimulating effect of patient serum was in the range of the CFU‐Eo stimulating effect of normal serum, after the addition of 5 u/ml of recombinant murine IL‐5. The results suggest that eosinophilia was caused by IL‐5 and GM‐CSF production by rhIL‐2 stimulated CD4 positive lymphocytes. The location on chromosomes 5 of the genes for IL‐5. GM‐CSF and IL‐3 may be associated with regulation of expression. by a common mechanism. of all the factors known to be involved in eosinophil production. This mechanism may be activated by IL‐2 stimulation. The separate location on chromosome 17 of the G‐CSF gene may explain the ability of IL‐2 to produce a distinct stimulus to eosinophil but not neutrophil production. Copyright © 1990, Wiley Blackwell. All rights reserved