Cyclosporin A and FK506 reduce interleukin-5 mRNA abundance by inhibiting gene transcription

Am J Respir Cell Mol Biol. 1997 Aug;17(2):243-50. doi: 10.1165/ajrcmb.17.2.2819.


The cytokine interleukin-5 (IL-5) selectively induces the proliferation, differentiation, and activation of mature eosinophils. The immunosuppressive agents cyclosporin A (CsA) and FK506 ameliorate the influx of eosinophils seen in allergic conditions such as asthma. We investigated the mechanisms controlling IL-5 messenger RNA (mRNA) expression in human T-lymphocytes in the presence of CsA or FK506. Fresh human peripheral blood mononuclear cells (PBMC); 7-day cultured PBMC, which represent a population of activated T-lymphocytes derived from PBMC; and the T-cell line HSB-2 were used. A novel polymerase chain reaction (PCR)-based nuclear run-on assay was employed to investigate the rate of IL-5 gene transcription. IL-5 mRNA degradation was measured by quantitative reverse transcriptase (RT)-PCR. CsA and FK506 strongly inhibited cellular IL-5 mRNA expression in response to phytohemagglutinin (PHA), or to phorbol myristate acetate (PMA), and/or calcium ionophore. Marked inhibition was observed in PBMC, 7-day cultured PBMC, and HSB-2 cells. Nuclear run-on assays done with either 7-day cultured PBMC or HSB-2 cells demonstrated striking inhibition of IL-5 gene transcription by both CsA and FK506 at levels reflecting the degree of reduction of total cellular IL-5 mRNA abundance. Neither CsA or FK506 had any detectable effect on the stability of IL-5 mRNA. Thus, the inhibitory effect of CsA and FK506 on cellular IL-5 mRNA expression can be explained by inhibition of the rate of IL-5 gene transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cyclosporine / pharmacology*
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-5 / genetics
  • Interleukin-5 / metabolism*
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Tacrolimus / pharmacology*
  • Transcription, Genetic / drug effects*
  • Tumor Cells, Cultured


  • Immunosuppressive Agents
  • Interleukin-5
  • RNA, Messenger
  • Cyclosporine
  • Tacrolimus