In vitro and in vivo characterization of the anti- inflammatory effects of cyclosporin A

Gianni Marone, Amato de Paulis, Vincenzo Casolaro, Anna Ciccarelli, Giuseppe Spadaro, Raffaele Cirillo

Research output: Contribution to journalArticlepeer-review

Abstract

Cyclosporin A (CsA), a cyclic undecapeptide extracted from Tolypocladium inflatum Gams, is effective in the prevention/treatment of graft rejection and in an increasing number of autoimmune and inflammatory disorders. The immunosuppressive effect of CsA was initially attributed to inhibition of lym- phokine mRNA transcription. We have demonstrated that pharmacological concentrations of CsA (10-100 ng/ml) also inhibit the in vitro immunologic release of preformed (histamine) and de novo synthesized (leukotriene C4 and prostaglandin D2) mediators of inflammatory reactions from human basophils and mast cells. Furthermore, the administration of a single dose of CsA (7 mg/ kg) to 8 normal donors caused a rapid and significant (20-40%) inhibition of histamine release from basophils obtained ex vivo from these subjects and challenged in vitro with anti-IgE, f-Met-Leu-Phe and A23187. The inhibitory effect of CsA peaked at 1-5 h, slowly decreased up to 13 h, and was associated with a sharp increase in blood CsA levels. Thus, CsA exerts remarkable anti-inflammatory effects on the immunologic release of mediators from human basophils and mast cells - properties that may contribute to the drug’s ther-apeutic effects.

Original languageEnglish (US)
Pages (from-to)279-283
Number of pages5
JournalInternational Archives of Allergy and Immunology
Volume99
Issue number2-4
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • Basophils
  • Cyclosporin A
  • Histamine
  • Leukotriene C<inf>4</inf>
  • Mast cells
  • Prostaglandin D<inf>2</inf>

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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