Differential regulation of IL-4 and IL-13 secretion by human basophils: Their relationship to histamine release in mixed leukocyte cultures

Angela C. Redrup, Brian P. Howard, Donald W. MacGlashan, Anne Kagey-Sobotka, Lawrence M. Lichtenstein, John T. Schroeder

Research output: Contribution to journalArticlepeer-review

Abstract

Human basophils are an important source of IL-4, a cytokine that is central to the pathogenesis of allergic inflammation. Recent reports have indicated that these cells also generate IL-13, which shares a number of biologic properties with IL-4. We found basophils to be the major source of IL-13 produced in mixed leukocyte cultures following 20-h activation with a variety of stimuli. While the magnitude of IL-4 protein generated correlated with the percent histamine secreted (r = 0.8; p = 0.007), there was no relationship between the levels of IL-13 detected and the amount of either IL-4 or histamine in cultures activated with IL-3/anti-IgE. The induction of IL-13 secretion also occurred in response to IL-3 alone, without concomitant secretion of either IL-4 or histamine. Although previously shown to inhibit IL-4 secretion, the phorbol ester PMA was a potent stimulus for IL-13 generation from basophils, and this secretion was sensitive to the protein kinase C inhibitor, bisindolylmaleimide. In contrast, bisindolylmaleimide did not prevent cytokine secretion induced by either anti-IgE or IL-3. The immunosuppressant, FK506, while strikingly inhibiting the accumulation of IL- 4 mRNA and the secretion of protein in response to IL-3/anti-IgE, had no effect on the generation of IL-13 in these cultures; the resistance was attributed to the IL-3-dependent signaling. Similarly, FK506 had no effect on the secretion of IL-13 in basophil cultures stimulated with PMA. This study suggests that multiple intracellular mechanisms control the generation of IL- 13 in basophils, some of which are distinct from those regulating IL-4.

Original languageEnglish (US)
Pages (from-to)1957-1964
Number of pages8
JournalJournal of Immunology
Volume160
Issue number4
StatePublished - Feb 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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