Longitudinal biobanks-based study on the joint effects of infections, nutrition and hormones on risk of prostate cancer.

Background To evaluate the individual and combined effects of enterolactone, vitamin D, free testosterone, Chlamydia trachomatis and HPV-18 on the risk of prostate cancer in a large population-based biochemical material that combined three Nordic serum sample banks. Material and methods A joint cohort of 209 000 healthy men was followed using cancer registry linkages. From this cohort altogether 699 incident cases of prostate cancer were identified. Four controls were selected by incidence density sampling and matching for country, age and date of the blood sampling. Complete data for all investigated exposures was available for 483 eligible cases and 1055 eligible controls. Multivariate regression analyses were performed to investigate the solitary and combined effects. Results The solitary effects were small. Significantly increased risk [rate ratio 1.6 (95% CI 1.0-2.5)] was found in those seronegative for C. trachomatis infection. The joint effect in risk levels of enterolactone and vitamin D was antagonistic [observed rate ratio (RR) 1.4 (1.0-2.1), expected RR 2.0 (1.0-4.1)] as well as that of HPV-18 and C. trachomatis [observed RR 1.9 (0.8-4.5), expected RR 9.9 (1.1-87.0)]. Conclusion A large follow-up study combining data from several previously investigated exposures to investigate joint effects found no evidence that exposure to two risk factors would increase the risk of prostate cancer from that expected on basis of exposure to one risk factor. If anything, the results were consistent with antagonistic interactions.

Influenza C virus infection in military recruits--symptoms and clinical manifestation.

Due to the lack of rapid diagnostic tests, clinical features of Influenza C virus infections are poorly characterized. Respiratory infections in military recruits in eastern Finland were monitored between July 2004 and December 2005 in order to study the epidemiology and clinical picture of infections caused by this virus. Blood samples were obtained at entry and at the end of the military service, and during each episode of respiratory infection to measure antibody responses against 10 viral and 2 bacterial pathogens. If possible, sputum samples were collected during the acute phase of respiratory infection episodes. Symptoms of the episodes were recorded for comparison of the clinical picture caused by various infectious agents. Infection with influenza C virus was detected in 38 of 892 young men during their service. The virus usually caused a mild upper respiratory tract infection. Most typical clinical features of influenza C virus infection were cough, rhinitis, and hoarseness. A striking difference to infections caused by influenza A virus was the lack of fever. Influenza C virus is an important cause of a respiratory tract infection in army conscripts. Infections with this virus are usually mild but can be complicated in some cases.

The effect of proatherogenic pathogens on adipose tissue transcriptome and fatty acid distribution in apolipoprotein E-deficient mice.

BACKGROUND: Chronic infections have been demonstrated to maintain low-grade systemic inflammation and associate with atherosclerosis. We studied the inflammation- and lipid homeostasis-related effects of Aggregatibacter actinomycetemcomitans (Aa) and Chlamydia pneumoniae (Cpn) infections on the epididymal and inguinal adipose tissue (AT) transcriptomes and fatty acid distribution in apolipoprotein (apo) E-deficient mice. Chow-fed apoE-deficient mice were exposed to 1) chronic intranasal infection with C. pneumoniae (Cpn group), 2) recurrent intravenous infection with A. actinomycetemcomitans (Aa group), 3) a combination of both types of infection (Cpn + Aa group), or 4) infection with the vehicle (control group). Epididymal and inguinal AT gene expression was analyzed using an Illumina Mouse WG-6 v2.0 platform and quantitative PCR (QPCR). Microarray data were analyzed using Gene Ontology enrichment analysis. AT fatty acid analysis was performed using gas-liquid chromatography. RESULTS: The transcriptomics data revealed significant enrichment in inflammation-associated biological pathways in both AT depots derived from the Aa and Cpn + Aa treated mice compared with the control group. The proportion of saturated fatty acids was higher in the inguinal AT in Aa (p = 0.027) and Cpn + Aa (p = 0.009) groups and in the epididymal AT in Aa group (p = 0.003). The proportion of polyunsaturated fatty acids was significantly lower among all Aa-infected groups in both depots. Chronic Cpn infection displayed only minor effects on transcriptomics and fatty acids of the AT depots. CONCLUSIONS: Systemic infection with A. actinomycetemcomitans activates inflammation-related biological pathways and modulates cellular lipid homeostasis. The adverse changes in adipose tissues during chronic infection may promote atherosclerosis.

Corn mint (Mentha arvensis) extract diminishes acute Chlamydia pneumoniae infection in vitro and in vivo.

Corn mint ( Mentha arvensis ) provides a good source of natural phenols such as flavone glycosides and caffeic acid derivatives, which may have prophylactic properties against inflammations. This study investigated whether corn mint extract would be beneficial against a universal respiratory tract pathogen, Chlamydia pneumoniae , infection. The extract inhibited the growth of C. pneumoniae CWL-029 in vitro in a dose-dependent manner. The inhibition was confirmed against a clinical isolate K7. The phenolic composition of the extract was analyzed by UPLC-ESI/Q-TOF/MS, the main components being linarin and rosmarinic acid. These compounds were active in vitro against C. pneumoniae. Linarin completely inhibited the growth at 100 µM. Inbred C57BL/6J mice were inoculated with C. pneumoniae K7. M. arvensis extract was given intraperitoneally once daily for 3 days prior to inoculation and continued for 10 days postinfection. The extract was able to diminish the inflammatory parameters related to C. pneumoniae infection and significantly (p = 0.019) lowered the number of C. pneumoniae genome equivalents detected by PCR at biologically relevant amounts.

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro.

Besides small molecules from medicinal chemistry, natural products are still major sources of innovative therapeutic agents for various conditions, including infectious diseases. Here we present the first attempt to design a combination treatment targeted against Chlamydia pneumoniae infection using coadministration of natural phenolics with calcium (Ca(2+)) modulators, and also the concomitant administration of these compounds with doxycycline. An in vitro acute C. pneumoniae model in human lung epithelial cells was used and Loewe additivity model was applied to evaluate the effects. In general, the phenolic compounds, quercetin, luteolin, rhamnetin and octyl gallate did not improve the antichlamydial effect of doxycycline, and, in some cases, resulted in antagonistic effects. The combination of doxycycline and Ca(2+) modulators (isradipine, verapamil and thapsigargin) was at most additive, and at subinhibitory concentrations of doxycycline, often even antagonistic. The Ca(2+) modulators showed no inhibitory effects on C. pneumoniae growth alone, whereas the coadminstration of Ca(2+) modulators with phenolic compounds resulted in potentiation of the antichlamydial effect of phenolic compounds. Verapamil (100 µM) was synergistic with low quercetin and luteolin concentrations (0.39 and 1.56 µM), whereas 10 µM isradipine was synergistic with high quercetin, rhamnetin and octyl gallate concentrations (12.5 µM and 100 µM). Use of thapsigargin with the phenolic compounds resulted in the most intense synergism. Interaction indices 0.12 and 0.14 were achieved with 0.39 µM luteolin and 10 and 100 nM thapsigargin, respectively. To conclude, the observed results indicate that the Ca(2+) modulators potentiate the antichlamydial effects of the phenolic compounds.

Antibodies to Chlamydia trachomatis in serum and peritoneal fluid of women with endometriosis.

The specifics of inflammation created by infection with Chlamydia trachomatis could be favourable to the genesis of endometriosis. To investigate this hypothesis, we studied the association between Chlamydia trachomatis specific IgG and IgA antibodies in serum and the peritoneal fluid of 51 women undergoing laparoscopic surgery. There was no significant difference between women with and without endometriosis with respect to the incidence of IgG and IgA in serum or the peritoneal fluid. The results of our preliminary study did not show any significant link between past infection with Chlamydia trachomatis and the presence of endometriosis.

The effect of proatherogenic microbes on macrophage cholesterol homeostasis in apoE-deficient mice.

BACKGROUND: Pathogens such as Aggregatibacter actinomycetemcomitans (Aa) and Chlamydia pneumoniae (Cpn) associate with an increased risk for cardiovascular diseases by inducing inflammation. We hypothesized that the pathogens affect the vascular wall by disturbing cholesterol homeostasis and endothelial function. METHODS: Aa- and Cpn-infections were induced in apoE-deficient mice by intravenous and intranasal applications, respectively. Cholesterol efflux from mouse peritoneal macrophages to apo(lipoprotein)A-I was assessed. The efflux capacity of mouse sera as acceptors of cholesterol from RAW264.7-macrophages was determined. Additionally, endothelial function was studied by following the relaxation capacity of rat mesenteric arteries after incubation in the conditioned culture media of the peritoneal macrophages isolated from the mice. RESULTS: Infection increased serum phospholipid transfer protein (PLTP) and lipopolysaccharide (LPS) activity, as well as serum amyloid A (SAA) and TNF-α concentrations. Peritoneal macrophages of mice with Aa-infection showed increased cholesterol uptake and reduced cholesterol efflux. Sera of Cpn and Cpn + Aa-infected mice had reduced cholesterol efflux capacity from RAW264.7-macrophages. Conditioned macrophage medium from mice with chronic C. pneumoniae infection induced endothelial dysfunction. Additionally, concentrations of serum adhesion molecules, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in Cpn-groups and E-selectin in Cpn + Aa-group, were elevated. The serum markers of endothelial function correlated positively with SAA. CONCLUSIONS: Aa- and Cpn-infections may generate proatherogenic changes in the vascular wall by affecting the macrophage cholesterol homeostasis and endothelial function.

Association of IL-6 and IL-6R gene polymorphisms with susceptibility to respiratory tract infections in young Finnish men.

Interleukin-1 (IL-6) is an important mediator of inflammatory response in the respiratory tract during an infection, and the action of IL-6 is mediated by an IL-6 receptor. Several polymorphisms in the IL-6 and IL-6R genes have been associated with different inflammatory disease states. We studied the association between 2 IL-6 (IL6A and IL6B) and 5 IL-6R gene polymorphisms (IL6R1 to IL6R5) and respiratory infections in 511 Finnish military recruits whose respiratory infectious episodes were followed during 6 months of service. A promoter polymorphism of the IL-6R gene, IL6R1 (-183G/A), and two intron 1 polymorphisms, IL6R2 (A/G) and IL6R3 (T/A), were associated with infections. The strongest associations were found for the IL6R1 and IL6R2 polymorphisms, which were in the same linkage disequilibrium block. Conscripts with the A/A (IL6R1), G/G (IL6R2), and A/A (IL6R3) genotypes had an increased risk for respiratory infections during service as follows: odds ratio (OR) 1.72, 95% confidence interval (CI) 1.35-2.19; OR 1.66, 95% CI 1.23-2.26; and OR 1.23, 95% CI 0.98-1.55, respectively. IL-6 gene polymorphism IL6A (-174C/G) was associated with infections only in combination with an IL-6R polymorphism. Our data suggest that polymorphisms in the 5' area of the IL-6R gene may be associated with increased susceptibility to respiratory infections.

Low mannose-binding lectin levels and MBL2 gene polymorphisms associate with Chlamydia pneumoniae antibodies.

OBJECTIVE: Mannose-binding lectin (MBL) has been shown to inhibit infection of host cells by Chlamydia pneumoniae in vitro. We studied if MBL levels and MBL2 polymorphisms associate with the presence of C. pneumoniae antibodies in vivo. MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs) of the MBL2 gene (promoter alleles H/L, X/Y and P/Q; and exon 1 variant alleles B, C and D and wild-type allele A) were genotyped and serum MBL concentrations and C. pneumoniae IgG, IgA and IgM antibodies were analysed in 889 Finnish military recruits. RESULTS: An MBL level below the median concentration and the MBL2 P/P genotype were significant risk factors of IgG or IgA seroconversions or the presence of IgM antibodies during military service (adjusted odds ratio (OR) 1.5; 95% confidence interval (CI) 1.1-2.1 and OR 1.5; 95% CI 1.0-2.2, respectively). In addition, the promoter Y/Y (OR 1.6; 95% CI 1.1-2.3) and exon 1 variant allele genotypes (OR 1.4; 95% CI 1.0-2.0) were possibly associated with elevated antibodies. CONCLUSIONS: These results suggest, for the first time, that low serum MBL levels and MBL2 polymorphisms may associate with elevated C. pneumoniae antibodies and seroconversions and thus support the previous findings in vitro.

Rapamycin can inhibit the development of Chlamydia pneumoniae, which might partly contribute to the prevention of in-stent restenosis.

BACKGROUND: Rapamycin, an immunosuppressive and antiproliferative drug, is used to prevent neointima formation to reduce the risk of in-stent restenosis with rapamycin eluting-stents. Chronic infection of Chlamydia pneumoniae has been associated with cardiovascular diseases, and could play an important role in the mechanism of restenosis. We examined the effect of rapamycin on the growth of C. pneumoniae in cell cultures. METHODS: HL cell monolayers were inoculated with C. pneumoniae CWL029 or C. trachomatis L2. Different concentrations of rapamycin were present in the culture medium continuously or for 8-hour periods. After incubation the infected cells were repassaged to fresh HL cell monolayers and incubated in the medium without rapamycin. The newborn inclusions from both passages were checked by fluorescent microscope or electron microscope. RESULTS: The presence of 23 microg/ml rapamycin restricted over 90% of the growth of C. pneumoniae. Continuous presence of 11 microg/ml rapamycin inhibited the growth of C. pneumoniae up to 80% and caused smaller inclusions, fewer chlamydial particles and fewer matured EBs. 11 microg/ml rapamycin presented in first passage caused the reduction of C. pneumoniae to 57% at first passage and 24% at second passage. CONCLUSIONS: Sufficient rapamycin can inhibit the growth of C. pneumoniae effectively, but it should be applied at the early stage of the chlamydial infections. Rapamycin eluting-stents can induce a high enough local concentration of rapamycin. This provides a possibility for us to suppose that the beneficial effect of rapamycin in preventing in-stent restenosis might partly be explained by its inhibitory effects on the growth of C. pneumoniae.

Quantification of Chlamydia pneumoniae in cultured human macrophages and HL cells: comparison of real-time PCR, immunofluorescence and ELISA methods.

Chlamydia pneumoniae is an intracellular gram-negative bacterium, which replicates only in eukaryotic cells. Quantification of C. pneumoniae in cell culture is needed when studying e.g. the effect of drugs or host cell factors on infectivity and replication. Conventionally, this has been performed by immunofluorescence staining and microscopic counting of chlamydial inclusions. However, this method is usable only if the cell numbers do not fluctuate in cell culture vials and the inclusions are uniform. In macrophages, inclusions are often aberrant, their sizes vary, and multiple inclusions are also seen. Therefore, methods are needed to quantify exact amounts of C. pneumoniae in cells. Here, we describe a new method based on the real-time PCR quantification of chlamydial genomes adjusted to the number of human genomes in cultures. In human epithelial (HL) cell cultures, the C. pneumoniae inclusion numbers and the ratio of C. pneumonia genomes/human genome (Cpn/Hum) correlated significantly (r = 0.978, p < 0.001); thus with HL cells, both methods are usable. However, in macrophage cultures, the correlation was weaker (r = 0.133, p = 0.036) and we recommend PCR quantification for exact measurements.

Chlamydia antibodies and self-reported symptoms of oligo-amenorrhea and hirsutism: a new etiologic factor in polycystic ovary syndrome?

OBJECTIVE: To investigate whether the systemic inflammation induced by chlamydial infections might be associated with symptoms of polycystic ovary syndrome (PCOS). DESIGN: Nested case-control study. SETTING: A questionnaire including questions about hirsutism and oligo-amenorrhea was distributed to a representative sample of women (at age 31) from the general population-based Northern Finland Birth Cohort. Those who reported both symptoms were defined as symptomatic (n=81). PATIENT(S): A representative sample of women (at age 31) from the general population-based Northern Finland Birth Cohort. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): To test the presence of serum antibodies to Chlamydia pneumoniae (IgG titers ≥32) and Chlamydia trachomatis (IgG titers ≥8) by microimmunofluorescence in symptomatic and control women. RESULT(S): Antibodies were investigated in 79 symptomatic and 1427 control women (C. pneumoniae) and in 79 symptomatic and 425 control women (C trachomatis). C. trachomatis antibodies (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3-4.6) and C. pneumoniae antibodies (OR, 1.5; 95% CI, 1.0-2.4) were more commonly present in symptomatic women, and the simultaneous presence of elevated highly sensitive C-reactive protein levels strengthened this association. CONCLUSION(S): Chronic inflammation, which is associated with chlamydial infections, could contribute to the pathogenetic processes that lead to the metabolic and hormonal disorders of PCOS.

Chlamydial lipopolysaccharide (cLPS) is present in atherosclerotic and aneurysmal arterial wall--cLPS levels depend on disease manifestation.

BACKGROUND: The role of Chlamydia pneumoniae in peripheral atherosclerosis disease and abdominal aortic aneurysm (AAA) remains unclear. Chlamydial lipopolysaccharide (cLPS) detection is a method used conventionally in routine chlamydial diagnosis of gynecological or ophthalmic samples. METHODS: We compared cLPS concentrations, as well as other markers of bacterial load, in plaques and sera of patients operated on for carotid artery stenosis (n=110), aorto-occlusive disease (n=22), or AAAs (n=50) at the Helsinki University Central Hospital. RESULTS: The median levels of cLPS in plaques were 2.28, 0.80, and 0.29 ng/ml in AAA, aorto-occlusive disease, and carotid artery stenosis patients, respectively (P<.001, Kruskal-Wallis). cLPS in serum correlated with LPS binding protein levels (Spearman's rho=0.52, P<.001), suggesting that the presence of chlamydiae is sufficient to produce an innate immune response reaction in these patients. Serum inflammatory markers interleukin 6 and highly sensitive C-reactive protein also correlate with cLPS (Spearman's rho=0.42 and 0.51, respectively, P<.001). CONCLUSIONS: cLPS is present in arterial disease, and the potential role of C. pneumoniae in the pathogenesis of both peripheral atherosclerosis disease and AAA should not be forgotten. cLPS has a positive correlation with serum inflammatory markers, but this is no proof of a causal association.

Serum chlamydial lipopolysaccharide as a prognostic factor for a new cardiovascular event.

BACKGROUND: Infections caused by Chlamydia pneumoniae are considered to participate in inflammatory processes leading to coronary artery disease. After a primary infection, the bacteria remain dormant intracellularly causing a chronic inflammatory stimulus. MATERIALS AND METHODS: Blood samples were obtained from 235 patients with acute myocardial infarction (AMI) and 108 patients with unstable angina pectoris (UA). We evaluated the prognostic significance of bacterial and viral antibody titers, serum troponin T, C-reactive protein, and chlamydial lipopolysaccharide (cLPS) concentrations during acute coronary syndrome of patients with AMI and UA for cardiovascular death and new UA and AMI that required hospital care during a 6-year follow-up. RESULTS: Serum cLPS levels correlated with C-reactive protein and serum troponin T concentrations during acute coronary events. Patients with AMI had significantly higher serum concentration of cLPS compared with patients with UA. Enterovirus antibody titers and cholesterol-lowering therapy at admission of the index event were negatively correlated with cLPS concentration (r = -.198, P = .0003 and r = -.26, P = .019, respectively). The presence of circulating cLPS was associated with a hazard ratio of 2.04 for a new cardiovascular event during the follow-up period (P = .006). The area under the curve in the receiver operating graph was .572. CONCLUSION: cLPS is evidently liberated from the infected atherosclerotic tissue during an acute coronary event. Our study supports the view that inflammation caused by C. pneumoniae infection is an important but as yet poorly understood factor in the development of atherosclerosis and may play a role in acute vascular events.

Chlamydial and periodontal pathogens induce hepatic inflammation and fatty acid imbalance in apolipoprotein E-deficient mice.

Periodontitis and Chlamydia pneumoniae infection are independent risk factors for cardiovascular diseases. The aim of this study was to investigate the effect of C. pneumoniae and Aggregatibacter actinomycetemcomitans infection on hepatic inflammation and lipid homeostasis of apolipoprotein E-deficient mice. Mice were infected with viable C. pneumoniae intranasally three times for chronic infection or once for acute infection. Viable A. actinomycetemcomitans was administered 10 times intravenously alone or in concert with C. pneumoniae. Hepatic alterations were assessed by histochemistry, lipid quantification, and fatty acid profile analysis. The RNA expression levels and the presence of pathogens in the livers and lungs were detected by quantitative real-time PCR. Both pathogens were detected in the livers of the infected animals. Chronic C. pneumoniae infection induced marked changes in hepatic lipid homeostasis. A. actinomycetemcomitans infection resulted in inflammatory cell infiltration into the liver, accompanied by elevated hepatic RNA expression levels of inflammation-related genes and higher serum amyloid A and lipopolysaccharide concentrations. Our results indicate that proatherogenic pathogens infect the liver, causing proinflammatory alterations and lipid disturbances. This infection may maintain chronic systemic inflammation attributable to atherogenesis.

Beneficial effect of clarithromycin in patients with acute coronary syndrome and complement C4 deficiencies.

OBJECTIVES: We sought to examine the role of complement component C4 deficiencies on the effect of antibiotic treatment in patients with acute coronary syndrome (ACS). DESIGN: Patients with ACS (n=144) were randomly divided to receive a three-month treatment of clarithromycin or placebo and followed for major adverse coronary and cerebrovascular events (MACCEs) for 404.5 median days (range 138-924 days). The primary results indicated that clarithromycin prevented recurrent cardiovascular attacks. For the present study we performed serum C4 allotyping of C4A and C4B. The clarithromycin response was reanalyzed taking into account the deficiencies in the C4 allotypes. RESULTS: The prevalence of C4A deficiency, C4B deficiency or these combined were 29.2% (42/144), 39.6% (57/144) and 66.0% (95/144), respectively. In patients with C4 deficiencies clarithromycin treatment resulted in a reduced number of MACCEs and the best cumulative survival as compared with the placebo group (MACCE 18.8% versus 39.1%, respectively; Log rank test, p=0.015). CONCLUSIONS: Only patients with ACS and C4 deficiencies seem to benefit from antibiotic treatment. This may explain the controversial results of secondary prevention trials of coronary artery disease and possibly serve as a pharmacogenomic marker for clarithromycin treatment.

Weight at birth and infancy in relation to adult leukocyte count: a population-based study of 5619 men and women followed from the fetal period to adulthood.

CONTEXT: Impaired fetal growth is associated with increased risk for coronary heart disease and diabetes in adulthood, but the underlying mechanism is unclear. OBJECTIVE: The objective of the study was to examine the relation between early growth (weight at birth and first year) and adult total leukocyte count, the primary cell effectors of inflammation. DESIGN: This was a birth cohort study (Northern Finland Birth Cohort 1966) with participants prospectively and longitudinally followed up from birth to age 31 yr. SETTING: This was a general population-based cohort in Finland. PARTICIPANTS: A total of 5619 offspring of expectant mothers who attended a clinical examination and blood draw at 31-yr follow-up (4486 with complete data on weight at 1 yr) participated in the study. MAIN EXPOSURE VARIABLES: Weight at birth and at 1 year. MAIN OUTCOME MEASURE: Absolute leukocyte count was measured. RESULTS: Total leukocyte count was lower at higher birth weight categories with or without adjustments for adult systolic blood pressure, total cholesterol, fasting insulin, body mass index, cigarette smoking, sex, gestational age, and other life course factors. The covariate-adjusted regression coefficient for log-transformed total leukocyte count (x 10(9) cells/liter) per 1 SD (525 g) increase in birth weight was -0.012 (95% confidence interval -0.021 to -0.004). The association persisted, even when limiting our analyses among healthy and nonsmoking individuals, and the inversely linear relation was steepest among those with lower weight attained at 1 yr (P for interaction = 0.027). CONCLUSION: Poorer growth in early life was associated with systemic low-grade inflammation in adulthood. This relation suggests a plausible inflammatory mechanism linking early growth impairment with risk of coronary heart disease and diabetes later in life.

Chlamydia pneumoniae DNA is present in peripheral blood mononuclear cells during acute coronary syndrome and correlates with chlamydial lipopolysaccharide levels in serum.

Chlamydia pneumoniae can possibly trigger and maintain inflammation in coronary arteries. Chlamydia pneumoniae DNA and chlamydial lipopolysaccharide (cLPS) were measured 3 times during a 1-y period in 97 patients with acute coronary syndrome. Chlamydia pneumoniae DNA in peripheral blood mononuclear cells was detected in 8 (8.2%) patients at the initial hospitalization and in 9 (10.6%) patients at 3 months. One y after the acute coronary syndrome, Chlamydia pneumoniae DNA was not found in any patients. Serum cLPS levels were elevated at inclusion, and declined significantly during follow-up (1.40 microg/ml; (0.20-2.91), median; (range of 25th to 75th percentiles) at inclusion, 0.44 microg/ml; (0.00-1.39) at 1 y; ANOVA p<0.0001). cLPS levels correlated significantly to Chlamydia pneumoniae DNA positivity at 3 months (p=0.003). In conclusion, Chlamydia pneumoniae DNA is present during acute coronary syndrome and in the recovery period, but declines in stable state, suggesting a role of the bacterium in the acute phase of coronary syndrome.

Chlamydial LPS and high-sensitivity CRP levels in serum are associated with an elevated body mass index in patients with cardiovascular disease.

OBJECTIVE: Seropositivity for Chlamydia pneumoniae has been associated with an elevated body mass index (BMI). Our aim was to study if serum chlamydial lipopolysaccharide (cLPS), C. pneumoniae antibodies and high-sensitivity C-reactive protein (hsCRP) levels are associated with BMI. PATIENTS AND METHODS: The study population consisted of 174 patients with symptomatic carotid stenosis, abdominal aortic aneurysm or occlusive aortic disease. Information on BMI, diabetes, smoking, hypercholesterolemia, and statin medication was available. Serum C. pneumoniae IgG and IgA antibodies, cLPS, hsCRP and total endotoxin activity (totLPS) were measured. RESULTS: BMI correlated with cLPS (r = 0.197; P < 0.01) and with hsCRP (rho = 0.195; P < 0.01); in addition, there was a positive correlation between cLPS and hsCRP (rho = 0.499; P < 0.01). A trend of an increasing proportion of C. pneumoniae IgG positivity (titre > or = 64; P = 0.018) and higher serum cLPS (P = 0.01) and hsCRP (P = 0.01) concentrations was observed across the BMI groups (BMI < or = 24.9 kg/m(2), BMI = 25.0-29.9 kg/m(2), and BMI > or = 30.0 kg/m(2)). Among the three BMI groups, 24.6%, 38.8%, and 48.3% were C. pneumoniae IgG-positive and the median (IQR) cLPS concentrations (ng/ml) of the groups were: 92.6 (50.8-167.0), 128.9 (76.4-163.9), and 146.4 (105.8-175.8), respectively. The median (IQR) hsCRP (mg/l) concentrations of the groups were: 1.70 (0.70-3.05) 1.70 (0.80-5.20), and 3.40 (1.45-8.55), respectively. These associations remained statistically significant in a multivariate analysis. CONCLUSIONS: Elevated serum cLPS levels were associated with an elevated BMI. This is a novel finding and it strengthens the link between chlamydial infection and obesity. A lack of association between totLPS and BMI suggests that the association between infection and an elevated BMI may be specific to certain pathogens.