ABSTRACT
The aim of our study was to investigate the combination of Chlamydophila pneumoniae and human cytomegalovirus (HCMV) as a pathogenic factor in atherosclerosis. Accordingly, we tested by means of PCR and immunohistochemistry the presence of these pathogens in the same atherosclerotic carotid specimen. The histology of the samples and the patients' antibodies against these pathogens were evaluated. Further, we examined the impact of C. pneumoniae and HCMV infection on the gene expression of the human monocytic cell line U937. Six of the 22 samples contained only C. pneumoniae, 4 contained only HCMV, 7 contained both C. pneumoniae DNA and/or antigens of both pathogens, and 5 samples were negative. No correlation was found between the presence of these microbes and either the cellular structure of the plaques, or the serostatus of the patients. The infection of U937 cells with HCMV and especially C. pneumoniae induced inflammation and atherosclerosis-related genes. Furthermore, the doubly-infected cells produced higher levels of the mRNA of pro-platelet basic protein and fatty acid binding protein 4. In conclusion, C. pneumoniae is often present in combination with HCMV in atherosclerotic carotid lesions. The in vitro coinfection model reveals that the doubly-infected monocytes are potent expressors of proatherosclerotic genes, suggesting that this coinfected population may accelerate the process of atherosclerosis.
Subject(s)
Carotid Stenosis/etiology , Chlamydophila Infections/complications , Chlamydophila pneumoniae/isolation & purification , Coronary Artery Disease/etiology , Coronary Vessels/microbiology , Cytomegalovirus Infections/complications , Cytomegalovirus/isolation & purification , Aged , Antigens, Bacterial/isolation & purification , Antigens, Bacterial/metabolism , Antigens, Viral/isolation & purification , Antigens, Viral/metabolism , Carotid Stenosis/microbiology , Carotid Stenosis/pathology , Carotid Stenosis/surgery , Cell Line , Chlamydophila Infections/diagnosis , Chlamydophila pneumoniae/genetics , Chlamydophila pneumoniae/immunology , Coronary Artery Disease/microbiology , Coronary Artery Disease/pathology , Coronary Artery Disease/surgery , Coronary Vessels/pathology , Coronary Vessels/surgery , Cytomegalovirus/genetics , Cytomegalovirus/immunology , Cytomegalovirus Infections/diagnosis , DNA, Bacterial/genetics , DNA, Viral/genetics , Endarterectomy, Carotid , Female , Humans , Immunohistochemistry , Male , Middle Aged , Monocytes/metabolism , Monocytes/microbiology , Monocytes/virology , Polymerase Chain Reaction , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , beta-Thromboglobulin/genetics , beta-Thromboglobulin/metabolismABSTRACT
The methylxanthine derivative pentoxifylline, widely used in the treatment of vascular diseases, also has numerous immunological effects. In in vitro experiments, the human natural killer cell cytotoxicity was investigated in the presence of pentoxifylline. A clinical trial involved an investigation of the natural killer cell activity in patients to whom pentoxifylline had been administered for different periods. The natural cytotoxicity in macroangiopathic patients treated with pentoxifylline was compared with that in healthy controls and that in patients with vascular diseases who did not receive pentoxifylline therapy. A total of 62 macroangiopathic patients and 20 healthy controls were investigated. The natural killer cell activity in patients receiving pentoxifylline therapy for more than a year proved to be significantly lower (P<0.005). The presence of vascular disease did not influence the natural killer activity. In the in vitro cytotoxicity reaction, pentoxifylline at a concentration of 100 microg/ml was found to suppress the natural killer cell cytotoxicity at any stage of the reaction. The influence of pentoxifylline on the natural killer cell activity was not due to inhibition of the expression of intercellular adhesion molecule-1. However, this drug significantly decreases (P<0.05) the apoptosis of target cells. It is presumed that the suppressor effect of pentoxifylline on natural killer cell activity should be taken into consideration in the treatment of clinical diseases where this drug is administered chronically.
Subject(s)
Intercellular Adhesion Molecule-1/drug effects , Killer Cells, Natural/drug effects , Pentoxifylline/pharmacology , Vascular Diseases/physiopathology , Vasodilator Agents/pharmacology , Adult , Apoptosis/drug effects , Dose-Response Relationship, Drug , Female , Fluorescent Antibody Technique , Humans , Intercellular Adhesion Molecule-1/genetics , K562 Cells/drug effects , Killer Cells, Natural/physiology , Male , Middle Aged , Tumor Necrosis Factor-alpha/analysisABSTRACT
Pentoxifylline used in the treatment of vascular diseases has also some immunological effects. Among of these effects the influence of pentoxifylline on the natural killer cell activity was studied. In in vitro experiments the human natural killer cell cytotoxicity was examined in the presence of pentoxifylline. In our clinical trial we investigated the topic whether this drug has an immunomodulatory effect while administering it for different periods. The natural cytotoxicity of macroangiopathic patients treated with pentoxifylline was compared with the values of healthy controls and patients suffering from vascular disease and obtaining no pentoxifylline therapy. Sixty two macroangiopathic patients and twenty healthy controls were investigated altogether. In the in vitro natural killer cell reaction we found that the pentoxifylline was able to suppress the cytotoxicity at any time of the reaction. The influence of pentoxifylline on natural killer cell activity was neither due to the expression of intercellular adhesion molecule-1, nor to the alteration of membrane fluidity. However, this drug significantly (p < 0.05) decreases the apoptosis of target cells. The natural killer cell activity of patients with chronic pentoxifylline therapy lasting for more than a year was proved to be significantly (p < 0.005) lower. The presence of vascular disease does not influence the natural killer activity by itself. Concluding our results we can state that the suppressing effect of pentoxifylline on natural killer cell activity needs to be taken into consideration in case of clinical diseases where this drug is administered chronically.
