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

Yuan, S

Some people may argue that CsA is a typical immunosuppressive agent and may weaken the body's resistance to AIV. However, considering that avian influenza causes an excessive immune response, it could be speculated that appropriately regulated immunity does not hamper the body's normal resistance to AIV. In fact, CsA affects influenza A virus M1 protein and inhibits the nuclear export of viral mRNA, and subsequently inhibits virus replication. 38 Previous studies reported that acute lung injury caused by chemical or microbial insults was secondary to the generation of host-derived, oxidized phospholipid that could potently stimulate Toll-like receptor 4 (TLR4)-dependent inflammation. 39 A recent study has shown that the TLR4 antagonist Eritoran protects mice from lethal influenza infection. 40 Eritoran is an alternative immunomodulator (besides CsA, Celecoxib and Mesalazine, as mentioned above) for controlling the influenza-associated inflammation (Figure 3) . Eritoran was originally designed as a drug for septicemia. The recent report showed that the survival rate of PR8 (a mouse-adapted influenza)-infected mice could reach 90% by the Eritoran treatment (if the mice were administered up to 6 days after influenza infection), 40 indicating its strong immunomodulatory properties (may be stronger than all other immunomodulators). However, Eritoran has not been used formally clinically so far, and it has been observed that it may cause some notable side effect of a dose-dependent incidence of phlebitis. 41 Similar to CsA, TLR4 also has a central role in IR injuries, 42,43 which might suggest a similarity between AIV-induced inflammatory reactions and IRmediated immune responses.