Drugs to cure avian influenza infection – multiple ways to prevent cell death

Yuan, S

CsA also inhibits calcineurin activity. 31 Calcineurin is a key enzyme in T-cell activation, which can stimulate the transcription of NF-AT (T-cell-specific transcription factor) and NF-IL-2A (IL-2 promoter elements). 32 Thus, CsA blocks the activation of T cells and suppresses the generation of a variety of cytokines, such as IL-2 and IFNs. 32 CsA could not be replaced by FK506, because CsA works not only as an immunosuppressant (similar to FK506) 31-33 but also as a protectant for maintaining the integrity of the mitochondrial membrane. 18 Nevertheless, many side effects were found for CsA, for example, renal tubular toxicity and vascular-interstitial lesions. Thus, its substitutes (some small-molecule chemical compounds) have been developed recently, such as Debio-025 and GW5. 34, 35 However, none of them has been used clinically so far. CsA only shows its apparent side effects after a long-term use (usually over a year). 36 Hence, for the current AIV therapy (usually within a month), CsA could be used expediently.