Effects of CAPE-like compounds on HIV replication in vitro and modulation of cytokines in vivo.
OBJECTIVE
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)-gamma, 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.
Department of Dentistry, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan, ROC.
Chuan-Chen
CC
Ho
Shih-Shen
SS
Lin
Ming-Yung
MY
Chou
Fang-Lung
FL
Chen
Chao-Chin
CC
Hu
Chung-Shih
CS
Chen
Guan-Yu
GY
Lu
Chi-Chiang
CC
Yang
D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D002109:Caffeic Acids; D016207:Cytokines; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol