JAC Advance Access originally published online on July 7, 2005
Journal of Antimicrobial Chemotherapy 2005 56(2):372-379; doi:10.1093/jac/dki244
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Effects of CAPE-like compounds on HIV replication in vitro and modulation of cytokines in vivo
1 Department of Dentistry, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan, R.O.C.; 2 Department of Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan, R.O.C.; 3 Institute of Immunology, Chung Shan Medical University, Taichung, Taiwan, R.O.C.; 4 Department of Pharmacy, Kuang Tien General Hospital, Taichung, Taiwan, Taiwan, R.O.C.; 5 School of Medical Technology, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
Received 11 March 2005; returned 16 May 2005; revised 31 May 2005; accepted 8 June 2005
* Corresponding author. Tel: +886-4-24730022, ext. 11716; Fax: +886-4-23767469; E-mail: cyang{at}csmu.edu.tw
Objectives: Five CAPE-like compounds, namely caffeic acid phenethyl ester (CAPE), methyl caffeate (MC), ethyl 3-(3,4-dihydroxyphenyl)acrylate (EC), phenethyl dimethyl caffeate (PEDMC) and phenethyl 3-(4-bromophenyl)acrylic (BrCAPE) were tested for their anti-HIV replication in vitro and immune modulation effects in vivo.
Methods: Short-term cytotoxicity was assessed by Trypan Blue stain and MTT assay. For antiviral assays, M-tropic (strain JRCSF), T-tropic (strain NL-4-3) and dual tropic (strain 89.6) HIV isolates were used in peripheral blood mononuclear cell (PBMC) culture.
Results: None of these CAPE-like compounds showed significant cytotoxicity in the treatment of PBMCs. By P24 EIA tests, CAPE, MC and EC significantly inhibited HIV replication in PBMC cells, but PEDMC and BrCAPE showed only slightly inhibitory effects. The in vivo modulatory effects on six cytokines [interleukin (IL)-2, IL-4, IL-6, interferon (IFN)-
, granulocyte-macrophage colony-stimulating factor (GM-CSF) and soluble Fas] were analysed. BALB/c mice treated with different doses or not treated with these CAPE-like chemicals showed that cytokines were increased to different extents by the different treatments. However, the concentrations of IL-6 and GM-CSF were not significantly affected by administration of any of these compounds (P > 0.05).
Conclusions: The different effects of treatments on anti-HIV replication and cytokine modulation suggested that these compounds affect virological and immunological response via different mechanisms. The virological and immunological mechanisms and response to these treatments need to be elaborated in further studies in order to derive the structural features of more effective compounds. Since neither death nor pathological change in the mice were observed in this study, these CAPE-like compounds are worth studying further as potential chemotherapy agents for anti-HIV infection and cytokine modulation.
Keywords: cytotoxicity , integrase inhibitors , chemotherapy