Infection, antibiotics, and atherothrombosis--end of the road or new beginnings?
- SourceAvailable from: Jens Kastrup[Show abstract] [Hide abstract]
ABSTRACT: The association observed between coronary heart disease (CHD) and Chlamydia (Chlamydophila) pneumoniae antibodies prompted, during the 1990s, several primary and secondary prevention trials with various antibiotics. In our CLARICOR trial, a randomized placebo-controlled trial in 4372 patients with stable CHD, a brief clarithromycin regimen was followed, unexpectedly, by increased long-term mortality. We now compare C. pneumoniae antibody levels at entry with population levels, with the patients' individual histories, and with their subsequent outcomes. IgG antibody levels were somewhat raised, but elevated IgA and IgG titers were unrelated to entry data (including prior acute myocardial infarction), except for an association with smoking and with not using statins. Hazards of mortality and of other outcomes tended to slightly increase with IgA and decrease with IgG titers, but the unfavorable clarithromycin effect was unrelated to antibody levels and remains unexplained. Smoking-related lung disease probably underlies the link between heart disease and increased IgG titers.Diagnostic microbiology and infectious disease 04/2010; 66(4):385-92. DOI:10.1016/j.diagmicrobio.2009.11.011 · 2.57 Impact Factor
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ABSTRACT: Since its description in 1986, Chlamydia pneumoniae has remained one of the most enigmatic pathogens. This intracellular bacterium is highly seroprevalent, but rarely recovered from cell culture, it can genetically switch between a proliferative and a nonreplicative state and has been linked to a vast number of chronic diseases, most notably to atherosclerosis, as it can be found in the plaques. It has become quite clear that persistent bacteria in atherosclerotic lesions cannot be eradicated by currently available antibiotic treatments and that attempts to do so without a better understanding of the pathobiology of chlamydial persistence are futile. However, there is growing knowledge on how vascular chlamydial infection may lead to the pathological reprogramming of the host cell signaling pathways. Chlamydia pneumoniae is now well known to induce, at least in vitro, the two pathogenetic main events that define atherosclerosis: angiogenesis and inflammation. In vivo a contribution of chlamydial infection to the progression of atherosclerosis remains unproven. This minireview provides a brief overview on the proproliferative and proinflammatory effects of vascular C. pneumoniae infection and their potential link to atherogenesis.FEMS Immunology & Medical Microbiology 04/2009; 55(2):131-9. DOI:10.1111/j.1574-695X.2008.00514.x · 2.55 Impact Factor
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ABSTRACT: Inflammation is considered a response set by the tissues in response to injury elicited by trauma or infection. It is a complex network of molecular and cellular interactions that facilitates a return to physiological homeostasis and tissue repair. The individual response against infection and trauma is also determined by gene variability. Ageing is accompanied by chronic low-grade inflammation state clearly showed by 2-4-fold increase in serum levels of inflammatory mediators. A wide range of factors has been claimed to contribute to this state; however, the most important role seems to be played by the chronic antigenic stress, which affects immune system thorough out life with a progressive activation of macrophages and related cells. This pro-inflammatory status, interacting with the genetic background, potentially triggers the onset of age-related inflammatory diseases as atherosclerosis. Thus, the analysis of polymorphisms of the genes that are key nodes of the natural immunity response might clarify the patho-physiology of age-related inflammatory diseases as atherosclerosis. On the other hand, centenarians are characterized by marked delay or escape from age-associated diseases that, on average, cause mortality at earlier ages. In addition, centenarian offspring have increased likelihood of surviving to 100 years and show a reduced prevalence of age-associated diseases, as cardiovascular disease (CVD) and less prevalence of cardiovascular risk factors. So, genes involved in CVD may play an opposite role in human longevity. Thus, the model of centenarians can be used to understand the role of these genes in successful and unsuccessful ageing. Accordingly, we report the results of several studies in which the frequencies of pro-inflammatory alleles were significantly higher in patients affected by infarction and lower in centenarians whereas age-related controls displayed intermediate values. These findings point to a strong relationship between the genetics of inflammation, successful ageing and the control of cardiovascular disease at least in men, in which these studies were performed. These data are also briefly discussed in the light of antagonistic pleiotropy theory and in order to pursuit a pharmacogenomics approach.Mechanisms of Ageing and Development 02/2007; 128(1):83-91. DOI:10.1016/j.mad.2006.11.015 · 3.51 Impact Factor