Cytomegalovirus (CMV) is one of the most important infections in the immunosuppressed patient. CMV disease often remains a life-threatening complication. In addition, studies have suggested a role for this virus as a contributing factor in allograft rejection. In the absence of any preventative therapy, CMV infection occurs in approximately 30 to 75% of transplant recipients, with an incidence of CMV disease between 8 and 80%. CMV infection may cause indirect effects, including acute and chronic re-infection, increased risk of cardiac complications, diabetes, and even death. Several drugs have been developed and approved for CMV treatment.
Apoptosis is programmed cell death, and is a multicellular animal life activity through gene regulation. Apoptosis mechanisms and the relationship of apoptosis with disease has become a hot topic in the field of biomedical research. Early stages of HCMV infection can block the apoptosis pathway to ensureviral protein synthesis, assembly and replication, resulting in persistent infection. HCMV infection increases the host cell apoptotic loss of cell function, leading to clinical symptoms. HCMV occurs mainly through the endogenous pathway to promote apoptosis
, and p53 is an apoptosis regulatory factorthat plays an important role.
LEF is an inhibitor of protein kinase activity, and is an immunosuppressive drug used in rheumatoid arthritis and organ transplantation. Many reports have described the benefit of LEF for CMV infection and clinical use
[6, 7]. LEFis currently under discussion for use as an antiviral substance in the clinic, because of its inhibitory effects on several viruses. LEF is cheaper and is easily given orally compared with other antivirals. LEF works via a novel mechanism and also has immunosuppressive properties. This study also found that LEF was effective in CMV infection. Given these considerations we believe that LEF is an exciting new drug for CMV infection. An American study showed that 88% of kidney transplant recipients suffered CMV infection
. Many studies have shownthat the meaningful value of LEF lies in its organ transplantation, bone marrow transplantation and hematopoietic stem cell transplant recipients with CMV infection
. In addition, animal experimentsof CMV confirmed that after treatment usingLEF the intracellular levels were significantly decreased by 75 to 99%
. LEF treated active rheumatoid arthritis patients with the HLA-DRB1 gene
. Recent studies have shown that LEF can reduce CMV infection of transplant recipients
. In addition, rheumatoid arthritis, systemic lupus erythematosus, glomerular diseases, skin diseases and other therapeutic areas also achieved good results. It is encouraging that LEF in the treatment of HCMV infection has also been a widespread concern
. The first report stated that LEF has anti-HCMV effects in renal transplant recipients. Recent clinical studies have shown that LEF has a better therapeutic effect on HCMV infection disease after renal transplantation and reduces viremia, promotes the involvement of organ function recovery, and increases sensitivity to GCV in mice with HCMV infection
[14–16]. LEF has a significant effect on refractory retinitis after allogeneic bone marrow transplantation in drug-resistant HCMV infection
[17–19]. Some studies have shown that the LEF has a good effect on the stubborn resistance of HCMV infection
In this study, we observed that cell proliferation was significantly inhibited by HCMV at 24 hours and 48 hours. With increasing HCMV concentrations, the value-added inhibition of cells was significantly decreased compared with the control group, and was statistically significant (P <0.01). Meanwhile, treatment with LEF significantly improved cell proliferation at 24 hours and 48 hours, with statistical significance (P <0.05). The effect of human fetal lung cell proliferation at the different doses of LEF was still significant (P <0.05). In addition, the apoptosis rate of human embryonic lung fibroblasts infected with HCMV increased significantly at 24 hours, 48 hours and 72 hours, and as time goes on the apoptosis rate is increased; compared with the control group it was statistically significant (P <0.01). The apoptosis rate of the HCMV infection group decreased by adding LEF, and was statistically significant (P <0.05). This finding confirmed that LEF is an effective new treatment for CMV infection.