Anti chlamydia antibodies in patients with thoracic and abdominal aortic aneurysms

BACKGROUND: Chlamydia species are suspected of being involved in the pathogenesis and progression of aortic aneurysms. We investigated serum levels of Chlamydia antibodies in patients with thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA) compared to levels in healthy individuals. METHODS: We included 35 consecutive patients with TAA, 42 patients with AAA and 42 age- and sex-matched healthy controls in a case control study. Serum antibodies (IgM and IgG) against Chlamydia lipopolysaccharide (LPS), Chlamydia pneumoniae and Chlamydia trachomatis were measured by recombinant ELISA and quantified by measurement of optical density. RESULTS: Patients with TAA exhibited median immunoglobulin levels against Chlamydia LPS (IgM 0.090, IgG 0.266), C. pneumoniae (IgM 0.023, IgG 0.264) and C. trachomatis (IgG 0.247) comparable to those of healthy subjects [Chlamydia LPS IgM 0.209 (p = 0.1), IgG 0.301 (p = 0.2); C. pneumoniae IgM 0.051 (p = 0.07), IgG 0.516 (p = 0.1); C. trachomatis IgG 0.153 (p = 0.2)]. Patients with AAA had higher serum levels of IgG against Chlamydia LPS (0.560) compared to healthy individuals [0.301 (p = 0.04)], but no significant elevation of antibodies against C. pneumoniae [IgM 0.029 (p = 0.1), IgG 0.545 (p = 0.9)] and C. trachomatis [IgG 0.219 (p = 0.3)]. CONCLUSION: Thoracic aortic aneurysms were not associated with signs of Chlamydia infection or immunopathogenicity. In contrast, patients with abdominal aortic aneurysms exhibited elevated levels of immunoglobulin against Chlamydia LPS, reflecting an unspecific Chlamydia immunopathogenicity. However, elevated levels of antibodies against distinct Chlamydia species were also not found in AAA patients.     

Interaction between Chlamydia pneumoniae seropositivity, inflammation and risk factors for atherosclerosis in patients with severe coronary stenosis

OBJECTIVE: To investigate whether Chlamydia pneumoniae (Cpn) seropositivity in patients with suspected coronary artery disease (CAD) (n = 81) is associated with increases in markers of inflammation, the severity of coronary atherosclerosis, and traditional risk factors for cardiovascular events. MATERIAL AND METHODS: The severity of coronary atherosclerosis was ranked by Gensini score. Inflammation and endothelial dysfunction were evaluated using white blood cell counts and levels of high-sensitivity C-reactive protein (hs-CRP), ferritin, tumour necrosis factor-alpha (TNF-alpha), interleukins 1beta and 6 (IL-1beta, IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), E-selectin and oxidized LDL (oxLDL), and these were compared between Cpn-seropositive and seronegative individuals. RESULTS: IgA and IgG Cpn seropositivity were significantly associated with the presence of CAD (p = 0.005) and were independent predictive factors for the severity of coronary atherosclerosis (p = 0.005). Elevated levels of IL-6 (p = 0.027) and triglyceride (p = 0.038) and low levels of high-density lipoprotein cholesterol (HDL-C) (p = 0.038) were significantly predicted by Cpn IgA and IgG seropositivity. CONCLUSIONS: Seropositivity for Cpn is a risk factor for patients with significant angiographically documented coronary stenosis. Additionally, Cpn seropositivity was significantly associated with dyslipidemia and elevated IL-6, known risk factors for CAD. These observations indicate that Cpn infection may be one entry point to the causal or contributory pathways that lead to atherosclerosis and its clinical manifestations.     

Increased levels of markers of vascular inflammation in patients with coronary heart disease

Elevated levels of soluble cell adhesion molecules (sCAMs), inflammatory cytokines and C-reactive protein (CRP) have been associated with atherosclerotic disease states. The aim of the present study was to evaluate whether circulating levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E- and P-selectin were significantly elevated in patients with coronary heart disease (CHD) compared with healthy controls, and to study possible associations between these sCAMs, tumour necrosis factor alpha (TNFalpha). interleukin-6 (IL-6), CRP and major CHD risk factors. The study included 193 patients in various stages of CHD and 193 matched controls. To evaluate any possible influence of acute phase reaction, reinvestigation was performed after 6 months. After adjustment for major CHD risk factors, sVCAM-1, sICAM-1, P-selectin, IL-6 and CRP remained significantly elevated in the CHD patients (p for all <0.001). In multivariate analysis sVCAM-1 was predicted by age (p=0.015), sICAM-1 by smoking (p<0.001) and total cholesterol (p=0.026), E-selectin by body mass index (BMI) (p=0.004) and P-selectin by male gender (p=0.015). TNFalpha significantly predicted sICAM-1 and E-selectin levels, while IL-6 predicted CRP but none of the sCAMs measured. This might indicate that TNFalpha, but not IL-6, plays a major role in the regulation of sCAM levels in vivo.     

Effects of isolated limb perfusion with tumor necrosis factor-alpha on circulating levels of proinflammatory cytokines

Hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor-a (TNFalpha) and cytotoxic drugs is currently used for treatment of melanoma and sarcoma of the limbs. Tumor necrosis factor-alpha is involved in the systemic inflammatory response syndrome as a result of activation of inflammatory cells and production of bioactive substances. The goal of this study was to determine the circulating levels of proinflammatory cytokines and soluble adhesion molecules in 19 patients with limb melanoma or sarcoma undergoing ILP with (n = 9) or without TNFalpha (n = 10). The results obtained demonstrated that ILP with TNFalpha was responsible for a leakage of TNFalpha in the systemic circulation, followed by a rise in interleukin (IL)-6 and IL-8 levels within I h. Elevated soluble (s)P-selectin levels were found 1-3 h after ILP. Plasma sE-selectin peaked 6-9 h after ILP, and soluble vascular cell adhesion molecule (sVCAM) levels reached a maximum after 24 h. Significant correlations were observed among these variables, confirming the interdependence of all changes observed. On the other hand, ILP with cytotoxic drugs alone induced only a modest release of TNFalpha, which was not followed by an immediate rise in IL-6 and IL-8. Four of the 9 patients undergoing ILP with TNF had severe systemic toxicity. No association was found between systemic TNF levels and the clinical outcome, whereas elevated TNF perfusion levels as well as systemic IL-6 and IL-8 levels were constantly elevated in patients with severe toxicity. These results are suggestive of an important role of TNFalpha levels in the perfusion system (more than leakage of perfusate) in causing postoperative toxicity, although other ILP-related factors should not be excluded.     

Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation.

Administration of IL-11 prevented lethal graft-versus-host disease (GVHD) in a murine bone marrow transplant (BMT) model (B6 --> B6D2F1) across MHC and minor H antigen barriers (survival at day 50: 90 vs 20%, P < 0.001). Surpisingly, IL-11 administration polarized the donor T cell cytokine responses to host antigen after BMT with a 50% reduction in IFNgamma and IL-2 secretion and a 10-fold increase in IL-4. This polarization of T cell responses was associated with reduced IFNgamma serum levels and decreased IL-12 production in mixed lymphocyte cultures (MLC). In addition, IL-11 prevented small bowel damage and reduced serum endotoxin levels by 80%. Treatment with IL-11 also reduced TNFalpha serum levels and suppressed TNFalpha secretion by macrophages to LPS stimulation in vitro. IL-11 thus decreased GVHD morbidity and mortality by three mechanisms: (a) polarization of donor T cells; (b) protection of the small bowel; and (c) suppression of inflammatory cytokines such as TNFalpha. We conclude that brief treatment with IL-11 may represent a novel strategy to prevent T cell-mediated inflammatory processes such as GVHD.     

Increase of chlamydial LPS antibodies in patients with acute coronary syndrome without detection of chlamydial DNA in atherectomy samples.

BACKGROUND: Chlamydia pneumoniae, a respiratory pathogen, has been connected with the pathogenesis of coronary artery disease (CAD). Previous studies indicated a correlation between antibodies to chlamydial LPS and the risk of cardiovascular disease. The aim of this study was to determine whether C. pneumoniae plays a direct role in the pathology of acute coronary syndromes (ACS). METHODS AND RESULTS: Twenty-five consecutive patients (median age 56 years) with ACS (17 acute myocardial infarction, 8 unstable angina) were included in the study and underwent directional coronary atherectomy. Tissue and blood samples were subjected to conventional and real time polymerase chain reaction (PCR) for C. pneumoniae. Antichlamydial immunoglobulin A (IgA) and IgG were examined by LPS enzyme immunoassay (EIA) and microimmunofluorescence (MIF) at intervention and on days 20, 45 and 180 thereafter. DNA of C. pneumoniae was detected neither in atherectomy samples nor in peripheral blood. Serologic results with LPS EIA showed a rapid and significant increase in specific IgA and IgG within 20 days including seroconversion in six cases (4 IgA, 2 IgG). Positive IgA and IgG MIF levels (30% and 87%) remained stable throughout the observation period. CONCLUSIONS: We conclude that negative detection of chlamydial DNA excludes a direct role of chlamydia in ACS. Our findings of rapid LPS antibody increase suggest a role of chlamydial LPS antigen which appears to be released during the acute event e.g. from damaged tissue, indicating a renewed accessibility to the immune system. An indirect role of chlamydia in the further aetiologic process of CAD seems possible.     

Higher prevalence of Chlamydia pneumoniae seropositivity in Finnish twins compared with co-twins living in Sweden: relationships with markers of subclinical atherosclerosis

Mortality rates from coronary heart disease are lower in Swedish men and among Finnish migrants who have lived in Sweden for over 20 years than in men living in Finland. Sero-epidemiological studies, investigations of atheromatous plaque specimens, in vitro animal models and anti-chlamydial antibiotic trials have given support to the hypothesis that Chlamydia pneumoniae (Cpn) has a role in atherosclerosis. We investigated whether men with a similar genetic background but living permanently in Finland or Sweden have differences in the prevalence of Cpn seropositivity, and whether chronic Cpn infection is associated with markers of subclinical atherosclerosis. We measured anti-Cpn antibodies and ultrasonographic markers of subclinical atherosclerosis, including carotid intima-media thickness, carotid artery compliance and brachial artery flow-mediated dilatation, in a population of 76 migrant-discordant male twin pairs (152 men). The number of men with seropositivity to Cpn infection (defined as IgA>/=1:64 and IgG>/=1:128) was greater in Finland than in Sweden (21.5% compared with 10.5%; P =0.046). Cpn seropositivity accompanied by elevated C-reactive protein (CRP) levels (>1 mg/l) was associated with attenuated brachial artery flow-mediated dilatation (3.3+/-0.3%, compared with 5.5+/-0.4% in men with no signs of Cpn infection; P <0.001).Thus, among Finnish twin brothers discordant for migration to Sweden, the prevalence of Cpn seropositivity is higher for those living in Finland, and men with Cpn seropositivity combined with elevated CRP levels had attenuated endothelial function. These findings offer insight into the mechanism whereby chronic Cpn infection may increase the risk of coronary heart disease.     

Development of enzyme immunoassays to detect salivary sIgA to Chlamydia pneumoniae and Mycoplasma pneumoniae

Enzyme immunoassays (EIAs) for the detection of secretory IgA antibody (sIgA) to Chlamydia pneumoniae and Mycoplasma pneumoniae from saliva are described. The presence of salivary sIgA in healthy laboratory personnel (mean age 40, range 25-62 years) was detected using conjugates of antibodies directed against secretory and alpha-chain domains. The EIA results for the detection of C pneumoniae sIgA antibodies were confirmed by a sensitive microimmunofluorescence method used as a reference. Circulating IgA antibody levels in sera were also determined using commercial EIAs. Secretory IgA antibodies to both C pneumoniae and M. pneumoniae were detectable only from persons with positive or borderline circulating IgA antibodies. Moreover, C. pneumoniae sIgA was found in the saliva of a clinically healthy person whose serum IgA antibody levels had been constantly elevated during the past 7 years. In conclusion, because of their specificity the described methods could be used in further delineation of the role of anti-C pneumoniae and M. pneumoniae sIgA antibodies. However, owing to the unexpected high frequency of these antibodies in saliva of clinically healthy persons, it seems unlikely that a single sIgA measurement from saliva is diagnostically more powerful than a single IgA measurement from serum to study and interpret the involvement of these pathogens in chronic respiratory diseases.     

Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations

Soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin (termed sICAM-1, sVCAM-1 and sE-selectin respectively) are found in the plasma, and are elevated during inflammatory conditions in which there is increased expression of the cellular forms of the molecules on endothelial and other cells. sICAM-1, sVCAM-1 and sE-selectin concentrations were measured in the plasma of 140 healthy Caucasian subjects aged between 18 and 75 years (100 males/40 females). sICAM-1 concentrations varied between 59.9 and 299.7 ng/ml (median 150 ng/ml), sVCAM-1 concentrations varied between 222.8 and 1672.9 ng/ml (median 662 ng/ml) and sE-selectin concentrations varied between 12.4 and 90.3 ng/ml (median 45.5 ng/ml). There were significant positive linear correlations between age and the plasma concentrations of sICAM-1 (r=0.580; P<0.001) and sVCAM-1 (r=0.392; P<0.001), which were retained when the effects of gender, body mass index and fasting plasma triacylglycerol and total cholesterol concentrations were controlled for. The significant positive linear correlation between age and the plasma concentration of sE-selectin (r=0.234; P=0.027) was lost when other variables were controlled for. Male subjects <40 years of age had significantly lower plasma concentrations of both sICAM-1 and sVCAM-1 than males >55 years of age (both P<0.001), but the difference in plasma sE-selectin concentrations between the age groups did not reach significance (P=0.073). Subgroups of 16 males aged <40 years and 12 elderly subjects (>55 years of age) participated in a doubled-blind, placebo-controlled study of fish oil supplementation over 12 weeks. The level of eicosapentaenoic acid in plasma phospholipids did not change with placebo supplementation, but was significantly increased with fish oil supplementation in both young male and elderly subjects (median increase 200%). sICAM-1, sVCAM-1 and sE-selectin concentrations were unaffected by supplementation with placebo in either young male or elderly subjects. sICAM-1 concentrations were unaffected by fish oil supplementation. sE-selectin concentrations were significantly increased by fish oil supplementation in young males (P=0.043; median increase 38%), but fish oil tended to decrease plasma sE-selectin concentrations in the elderly subjects (P=0.075), with a median decrease of 11%. sVCAM-1 concentrations were unaffected by fish oil supplementation in young males. Fish oil supplementation significantly decreased plasma sVCAM-1 concentrations in the elderly subjects (P=0.043), with a median decrease of 20% (range 16-60%). These observations suggest that fish oil decreases endothelial activation in elderly subjects.     

Chlamydia antibody titers in patients with coronary disease: relations to age and clinical stage]

BACKGROUND AND AIM: Atherosclerosis and its clinical sequelae are responsible for the highest death rate in industrialized countries. Seroepidemiological, pathological and immunohistochemical studies have suggested a relation between Chlamydia pneumoniae infection and the development of coronary sclerosis. Aim of this study was to investigate the frequency distribution of Chlamydia pneumoniae antibody titers in patients with different clinical stages of coronary artery disease (CAD) and patients without CAD as well as a possible age dependence of antibody titers within the study groups. For this purpose, 522 consecutive patients of a cardiology ward were investigated, over a period of 10 months, for the presence of Chlamydia pneumoniae antibodies (IgG, IgA, IgM) using specific ELISA's. In general, there was no difference in the frequency of positive Chlamydia antibody titers between CAD patients and the control group. Only in the subgroup of unstable CAD-patients < 50 years a tendency of increased antibody titers was present. Patients with stable angina, unstable angina, or acute myocardial infarction exhibited no significant differences in the rate of infection between the different age groups (p < 0.117). In contrast, there was a significant increase in positive Chlamydia pneumoniae antibodies with increasing age in the control group (p = 0.002). The relatively high incidence of positive Chlamydia pneumoniae antibody titers in young CAD patients, which is associated with a loss of age-dependent increase of the antibody titers in the CAD group, might indicate a specific role of Chlamydia pneumoniae infections for the manifestation of premature CAD (before the age of 50). Due to the increased rate of Chlamydia pneumoniae infections with increasing age, the determination of Chlamydia pneumoniae antibody titers does not allow reliable conclusions on the infectious pathogenesis of CAD. Furthermore, our unability to demonstrate differences in antibody titers between CAD patients with stable angina, unstable angina, and acute myocardial infarction suggests that acute Chlamydia pneumoniae infections are not responsible for the development of acute coronary syndromes.     

Attenuation of catecholamine-induced immunosuppression in whole blood from patients with sepsis

Studies performed on healthy volunteers have revealed that catecholamines down-regulate the lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF)alpha, interleukin (IL)-6, and IL-1beta. We extended this observation and show that this effect is based on changes in the mRNA concentration of these cytokines. Catecholamines are increased in severe sepsis due to endogenous production and have to be administered exogenously when the disease has proceeded to the state of prolonged hypotension. We here investigated whether the immunomodulating effect of catecholamines could also be demonstrated in the blood of patients with prolonged severe sepsis and of those in prolonged septic shock. Blood was stimulated ex vivo with LPS in the presence and absence of epinephrine and the cytokine protein concentration was determined. In blood of healthy volunteers, epinephrine reduced the LPS-stimulated synthesis of TNFalpha by 62.5% (P< 0.0001), of IL-6 by 39% (P< 0.0001), and of IL-1beta by 40% (P= 0.015), and increased the LPS-stimulated IL-10 production by 77.8% (P < 0.0001). Correspondingly, in blood of patients with prolonged severe sepsis, TNFalpha was reduced by 67.2% (P < 0.0001) and IL-6 was reduced by 32.9% (P < 0.0001); IL-1beta and IL-10 were not modulated by catecholamines in these patients. In blood samples of patients in prolonged septic shock, epinephrine did not modulate cytokine levels of IL-6 and IL-10, and decreased TNFalpha only by 36.4% (P < 0.0001). Interestingly, epinephrine suppressed the IL-1beta production by 73% (P < 0.0001) in blood of patients in prolonged septic shock, which was twice as much as in blood samples of healthy volunteers. The altered response of septic blood to catecholamines might be due to an altered reactivity of leukocytes in the prolonged disease although an additional role of preexisting catecholamines cannot be completely excluded.     

Association of hyperhomocysteinemia and <Emphasis Type="Italic">Chlamydia pneumoniae</Emphasis> infection with carotid atherosclerosis and coronary artery disease in Japanese patients

An elevated plasma level of homocysteine (Hcy) and infection by Chlamydia pneumoniae (C. pneumoniae) have been suggested as independent risk factors for carotid atherosclerosis (CA) and coronary artery disease (CAD), but the mechanisms involved are unclear. We investigated the correlation between positivity for antibody to C. pneumonia (anti-C. pneumoniae) and the Hcy level in patients with CA and CAD. The total plasma homocysteine (tHcy) concentration was determined in 99 patients with CA and 31 patients with CAD, as well as 119 controls with matched risk factors for atherosclerosis. The tHcy level was measured with a Bio-Rad microplate enzyme immunoassay. In the CAD group, the tHcy level (13.67 micromol/l) was significantly higher than that in other groups (CA group, 10.96 micromol/l; control group, 9.95 micromol/l; ANOVA, P = 0.0006). Positivity for anti-C. pneumoniae IgG was significantly more common in the CAD group (77.4%) than in the other groups (CA group, 53.5%; control group, 54.6%; ANOVA, P = 0.0490). There was no association between anti-C. pneumoniae IgA positivity or tHcy and conventional risk factors. However, anti-C. pneumoniae IgG positivity was significantly more common in subjects with higher tHcy levels than in those with low tHcy levels from each of the 3 groups. The CAD group had significantly higher tHcy levels, and tHcy was significantly associated with anti-C. pneumoniae IgG positivity. These findings indicate that elevation of tHcy is related to positivity for anti-C. pneumoniae IgG in patients with CAD.     

Interaction between cytokines and sCD40L in patients with stable and unstable coronary syndromes

BACKGROUND: Evidence suggests that soluble CD40-ligand (sCD40L) is elevated in coronary artery disease (CAD) and is released from activated platelets during the acute myocardial infarction (AMI). Although sCD40L is part of immune response, the mechanisms regulating its release in different disease states remain unknown. MATERIALS AND METHODS: This study enrolled 596 subjects: 201 patients with stable CAD, 109 patients with AMI and 286 healthy controls. Circulating levels of sCD40L, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-a (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with AMI (n = 109) had higher levels of sCD40L and IL-6 compared to both CAD (n = 201) (P < 0.01) and controls (n = 286) (P < 0.01), while CAD also had higher levels of sCD40L and IL-6 compared to controls (P < 0.01). Similarly, sICAM-1 and sVCAM-1 levels were higher in CAD and AMI compared to controls (P < 0.05). IL-6 was the only parameter independently associated with sCD40L in healthy individuals [beta (SE):0.491(0.096), P = 0.0001]. However, in CAD or AMI, only diabetes mellitus [beta (SE): 2.689 (1.082), P = 0.044 and beta (SE): 10.406 (3.215), P = 0.002, respectively] and smoking [beta (SE): 3.470 (1.111), P = 0.002 and beta (SE): 9.694 (2.478), P = 0.0001, respectively] (but not IL-6), were independently associated with sCD40L levels. CONCLUSIONS: Both CAD and AMI are accompanied by increased levels of sCD40L in parallel with an elevation of proinflammatory cytokine IL-6 and adhesion molecules sVCAM-1 and sICAM-1. Diabetes mellitus and smoking (but not IL-6 or adhesion molecules) were the only factors independently associated with sCD40L levels in CAD and AMI patients.     

Metabolic syndrome aggravates the increased endothelial activation and low-grade inflammation in subjects with familial low HDL

BACKGROUND: Inhibition of cytokine-induced expression of adhesion molecules is one of the atheroprotective mechanisms of high-density lipoprotein (HDL). AIM: We investigated whether increased endothelial activation and low-grade inflammation are present in Finnish subjects with familial low HDL, and which factors contribute to the inflammatory parameters. METHOD: High-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were measured in 91 subjects with low HDL-cholesterol from 41 low-HDL families and in 112 normolipidemic controls with comparable age- and gender distribution. Presence of the features of the metabolic syndrome (MetS) was recorded. RESULTS: sVCAM-1, sICAM-1, sE-selectin, and hsCRP were significantly higher in low-HDL subjects than in the controls (sVCAM-1: 560+/-147 ng/mL versus 496+/-95 ng/mL, P = 0.001; sICAM-1: 247+/-60 ng/mL versus 215+/-47 ng/mL, P<0.001; sE-selectin: 52+/-20 ng/mL versus 44+/-16 ng/mL, P = 0.022; and hsCRP: 1.73+/-2.05 mg/L versus 0.85+/-1.10 mg/L, P<0.001). Low-HDL subjects had increased body mass index (BMI) and waist, and elevated insulin and triglyceride levels. Adhesion molecules and hsCRP increased according to the number of the features of the MetS. CONCLUSIONS: The presence of the MetS in subjects with familial low HDL-cholesterol aggravates the low-grade inflammation and endothelial activation, and ultimately may add to the higher susceptibility for atherosclerotic disease in these individuals.     

Soluble L-selectin level is a marker for coronary artery disease in type 2 diabetic patients

OBJECTIVE: To investigate whether the fall in soluble L-selectin (sL-selectin) level constitutes a marker for myocardial ischemia. RESEARCH DESIGN AND METHODS: The levels of soluble forms of adhesion molecules, i.e., intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), P-selectin (sP-selectin), and L-selectin (sL-selectin), were compared in type 2 diabetic patients without inflammatory syndrome but with symptomatic coronary artery disease (CAD) (group 1, n = 11), with silent ischemic disorders and proven coronary stenoses (group 2, n = 11), with silent myocardial ischemia (SMI) and normal coronary angiography (group 3, n = 10), and without proven SMI (group 4, n = 13). These levels were compared with those of 22 control subjects. RESULTS: The sL-selectin level was significantly lower in groups 1, 2, or 3 with symptomatic CAD or with SMI as compared with the control group (P = 0.0004). Group 4 without myocardial ischemia did not significantly differ from the control subjects (P = 0.6). In type 2 diabetic patients, after controlling for HbA1c, a partial correlation between sL-selectin and the CAD status was significant (P = 0.001). sICAM-1 and sP- or sE-selectin did not differ significantly between type 2 diabetic patients and control subjects or among the different groups of patients. The sVCAM-1 level in type 2 diabetic patients was significantly higher than in the control subjects (P = 0.001), but there were no significant intergroup differences (P = 0.4). CONCLUSIONS: In type 2 diabetic patients, sVCAM-1 is increased with regard to glycemic control, whatever the CAD status. In type 2 diabetic patients with symptomatic CAD or SMI associated with coronary stenoses, sL-selectin is significantly decreased. A marked fall in sL-selectin might constitute a marker for silent CAD in type 2 diabetic patients.     

Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model.

We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus. 55 Sprague-Dawley rats were randomized to either intravenous saline or lipopolysaccharide (LPS). After 50 min of spontaneous respiration, the lungs were excised and randomized to 2 h of ventilation with one of four strategies: (a) control (C), tidal volume (Vt) = 7 cc/kg, positive end expiratory pressure (PEEP) = 3 cm H2O; (b) moderate volume, high PEEP (MVHP), Vt = 15 cc/kg; PEEP = 10 cm H2O; (c) moderate volume, zero PEEP (MVZP), Vt = 15 cc/kg, PEEP = 0; or (d) high volume, zero PEEP (HVZP), Vt = 40 cc/kg, PEEP = 0. Ventilation with zero PEEP (MVZP, HVZP) resulted in significant reductions in lung compliance. Lung lavage levels of TNFalpha, IL-1beta, IL-6, IL-10, MIP-2, and IFNgamma were measured by ELISA. Zero PEEP in combination with high volume ventilation (HVZP) had a synergistic effect on cytokine levels (e.g., 56-fold increase of TNFalpha versus controls). Identical end inspiratory lung distention with PEEP (MVHP) resulted in only a three-fold increase in TNFalpha, whereas MVZP produced a six-fold increase in lavage TNFalpha. Northern blot analysis revealed a similar pattern (C, MVHP < MVZP < HVZP) for induction of c-fos mRNA. These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung, and thus may play a role in initiating or propagating a local, and possibly systemic inflammatory response.     

Soluble adhesion molecules in acute ischemic stroke

BACKGROUND: Inflammatory adhesion molecules play a key role in the development of ischemic lesions. Elevated plasma concentrations of soluble adhesion molecules are reported in stroke patients, but data are still controversial. Our aim was to explore the potential association of plasma levels of soluble (s) intercellular and vascular cellular adhesion molecules-1 (sICAM-1 and sVCAM-1), sE-selectin and sL-selectin with acute ischemic stroke. METHODS: At our university hospital in Zagreb, Croatia, we prospectively enrolled 67 subjects with acute ischemic stroke, as well as 76 consecutive healthy individuals as controls who were visiting the centre for reasons unrelated to stroke. Serum concentrations of the molecules of interest were determined by means of quantitative sandwich enzyme immunoassay. RESULTS: Mean levels of sICAM-1 (p < 0.001), sVCAM-1 (p < 0.034) and sE-selectin (p < 0.002) were higher in patients than in controls, whereas sL-selectin was lower in patients (p = 0.043). In patients, levels of soluble adhesion molecules were independent of age and sex except for sL-selectin, which was inversely correlated with age (r = -0.260, p = 0.034) and higher in women (p = 0.006) and diabetics (n = 14; p = 0.004). Serum levels did not differ significantly with respect to carotid atherosclerotic disease, smoking status, hypertension or hypercholesterolemia. As well as correlating with each other, concentrations of soluble adhesion molecules in patients correlated with traditional biochemical markers of inflammation: total leukocyte count, erythrocyte sedimentation rate (ESR) and C-reactive protein level. Concentrations of sICAM-1 and high-density lipoprotein-cholesterol and ESR were identified as significant independent predictors/indicators of acute ischemic stroke. CONCLUSIONS: Acute ischemic stroke is associated with elevated plasma levels of sICAM-1, sVCAM-1 and sE-selectin, independent of age, sex and other recognized risk factors for stroke. Decreased levels of sL-selectin are associated with acute stroke. The observed changes in serum concentrations of adhesion molecules indicate inflammatory process occurring during acute cerebral ischemia.     

Infection induced inflammation is associated with erectile dysfunction in men with diabetes

BACKGROUND: In diabetic patients with erectile dysfunction, endothelial dysfunction is a major underlying cause. Infection-induced inflammation may be associated with endothelial dysfunction. The goal of this study was to determine whether erectile dysfunction in patients with diabetes is associated with infections of Chlamydia pneumoniae or cytomegalovirus and/or with low-grade inflammation. MATERIALS AND METHODS: Diabetic patients, 57 with and 33 without erectile dysfunction, were enrolled in a case-control study. Both groups of patients consists of type 1 and type 2 diabetics. Serum antibodies against cytomegalovirus and C. pneumoniae and markers of inflammation, including high-sensitivity C-reactive protein and fibrinogen, were measured. RESULTS: Adjusted odds ratios for erectile dysfunction in cytomegalovirus IgG, C. pneumoniae IgG and C. pneumoniae IgA seropositive men were 2.4 (95%CI; 1.0-6.0), 3.0 (95%CI; 1.2-8.1) and 1.8 (95%CI; 0.7-4.6), respectively. Odds ratios for the highest tertiles of high-sensitivity C-reactive protein and fibrinogen concentrations compared to the lowest tertile were 4.3 (95%CI; 1.4-13.1) and 6.6 (95%CI; 2.1-21.2), respectively. CONCLUSION: Elevated high-sensitivity C-reactive protein or fibrinogen serum levels and infection with cytomegalovirus or C. pneumoniae were associated with erectile dysfunction in diabetes. The relation between cytomegalovirus and erectile dysfunction is markedly present in patients with elevated high-sensitivity C-reactive protein and fibrinogen levels, suggesting a modifying effect by the inflammation.