Interleukin-2 treatment-associated eosinophilia is mediated by interleukin-5 production

Br J Haematol. 1990 Oct;76(2):168-73. doi: 10.1111/j.1365-2141.1990.tb07867.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Eosinophilia / chemically induced*
  • Eosinophilia / immunology
  • Eosinophils / cytology
  • Eosinophils / drug effects
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • Immunotherapy
  • Interleukin-2 / adverse effects*
  • Interleukin-2 / pharmacology
  • Interleukin-2 / therapeutic use
  • Interleukin-5 / biosynthesis*
  • Interleukin-5 / blood
  • Leukemia, Myeloid, Acute / therapy*
  • Leukocytes / drug effects
  • Leukocytes / immunology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Male
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use

Substances

  • Interleukin-2
  • Interleukin-5
  • Recombinant Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor