title: Interleukin-2 treatment-associated eosinophilia is mediated by interleukin-5 production.
abstract: 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 x 10(9)/l before rhIL-2 to 0.98 x 10(9)/l within 48 h of stopping the infusion, and an exponential correlation between the pretreatment lymphocyte CD4:CD8 ratio and the maximum eosinophil count was observed. RhIL-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 CFU-Eo 12 times more than control serum (P less than 0.05). 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.
authors.affiliation: Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London.
authors.forename: D
authors.initials: D
authors.lastname: Macdonald
authors.forename: A A
authors.initials: AA
authors.lastname: Gordon
authors.forename: H
authors.initials: H
authors.lastname: Kajitani
authors.forename: H
authors.initials: H
authors.lastname: Enokihara
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004802:Eosinophilia / Q000139:chemically induced* / Q000276:immunology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000097:blood; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000097:blood; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007376:Interleukin-2; D015848:Interleukin-5; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor