**2. Mechanism of action**

Cyclosporin, an 11-amino acid, cyclic polypeptide produced from the fungal species *Beauveria nivea*, is a calcineurin inhibitor that acts selectively on T cells (Amor et al., 2010). Cyclosporin binds to the intracellular immunophilin cyclophilin to form a complex, which then binds to and inhibits the enzymatic activity of calcineurin phosphatase, a serine-

Fig. 1. Mechanism of cyclosporine action. Cyclosporine (CsA) binds to cyclophylin (CpN), forming a complex that binds and blocks the function of the enzyme calcineurin (CaN). As a result, CaN fails to dephosphorylate the cytoplasmic component of the nuclear factor of activated T cells (NF-ATc), and the transport of NF-ATc to the nucleus and the binding of NF-ATc to the nuclear component of the nuclear factor of activated T cells (NF-ATn). The NF-ATc–NF-ATn complex binds to the promoter of the interleukin 2 (IL-2) gene and initiates IL-2 production. Consequently, T cells do not produce IL-2, which is necessary for full T-cell activation.(Modified from Stepkowski, S.M. 2000)

cyclosporin preparation, and of avoiding any confusion between the various cyclosporin formulations available (Colombo & Egan, 2010). Indeed, a Canadian survey reported that up to 20% of new cyclosporin recipients may be given a cyclosporin formulation different from

The efficacy of cyclosporin in well-designed, randomised controlled trials, with

Cyclosporin, an 11-amino acid, cyclic polypeptide produced from the fungal species *Beauveria nivea*, is a calcineurin inhibitor that acts selectively on T cells (Amor et al., 2010). Cyclosporin binds to the intracellular immunophilin cyclophilin to form a complex, which then binds to and inhibits the enzymatic activity of calcineurin phosphatase, a serine-

Fig. 1. Mechanism of cyclosporine action. Cyclosporine (CsA) binds to cyclophylin (CpN), forming a complex that binds and blocks the function of the enzyme calcineurin (CaN). As a result, CaN fails to dephosphorylate the cytoplasmic component of the nuclear factor of activated T cells (NF-ATc), and the transport of NF-ATc to the nucleus and the binding of NF-ATc to the nuclear component of the nuclear factor of activated T cells (NF-ATn). The NF-ATc–NF-ATn complex binds to the promoter of the interleukin 2 (IL-2) gene and initiates IL-2 production. Consequently, T cells do not produce IL-2, which is necessary for

full T-cell activation.(Modified from Stepkowski, S.M. 2000)

This chapter will review the following with respect to psoriasis treatment:

important economic information from certain key clinical trials

that actually prescribed (Davies & Gupta 2000).

The pharmacokinetic properties of cyclosporin

The role of cyclosporin in current combination therapy

The mechanism of cyclosporin action

Side effects of the compound.

**2. Mechanism of action** 

threonine phosphatase that depends on calcium and calmodulin for activity (Amor et al., 2010; Giese et al., 2004; Stepkowski 2000). Consequently, calcineurin cannot dephosphorylate an important transcription factor: the cytoplasmic component of nuclear factor of activated T cells (NF-ATc) [Fig.1]. Transport of NF-ATc to the cell nucleus, and binding of NF-ATc to the promoter region of the IL-2 gene nuclear component of NF-AT (NF-ATn), is therefore blocked and T cells can no longer produce IL-2, a cytokine required for complete activation of the T-cell pathway, granulocyte-macrophage colony-stimulating factor, and interferon-γ production (Amor et al., 2010; Giese et al., 2004). The consequences of cyclosporin action include (Amor et al., 2010):

