Cyclosporine and the human regulatory cells

Αναστασόπουλος Γεώργιος

Ωτορινολαρυγγολόγος, Αθήνα

Cyclosporine, Κυκλοσπορίνη.  Cyclosporine (CsA) is a cyclic peptide produced by the fungus Tolypocladium inflatum Gams; It is an immunosuppressive drug, relatively specific for regulating the function of helper T cells by blocking gene transduction for IL2. Cyclosporine binds to a cytoplasmic protein called cyclophiline, an enzyme that inhibits the formation of tertiary structures of proteins involved in signal transduction to the nucleus. Unlike cytotoxic immunosuppressants cyclosporine, in therapeutic concentrations do not cause myelosuppression. Cyclosporine is used primarily in combination with prednisone to sustain renal, hepatic, and cardiac transplants. It has helped the success of bone marrow transplantation from siblings and parents to 50%-80%. Preliminary results suggest that cyclosporine might be of benefit in some patients with steroid dependent asthma. Cyclosporin is used against autoimmune diseases such as, uveitis, psoriasis, diabetes mellitus, rheumatoid arthritis and some types of nephropathy. Limiting factors in the future use of cyclosporin in asthma, are the side-effects particularly renal and hepatic damage [1, 2]. CsA significantly impaireσ the function of CD4+CD25+ Treg cells by inducing interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) secretion. CsA may block the induction of immune tolerance and decrease the risk of hepatitis C recurrence [3].

1. Kahan, B.D.: Cyclosporin, N. Engl. J. Med. 1989;32:1725-38.

2. Srczeklik, A., et al: Cyclosporine for steroid-dependent asthma. Allregy (1991) 46, No. 4, p. 312-315.

3. Miroux C, Moralès O, Carpentier A, Dharancy S, Conti F, Boleslowski E, Podevin P, Auriault C, Pancré V, Delhem N. Inhibitory effects of cyclosporine on human regulatory T cells in vitro. Transplant Proc. 2009 Oct;41(8):3371-4.