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Dendritic cell toll-like receptors (TLRs) and the high-affinity immunoglobulin E (IgE) receptor (FcεRI) may biologically interact with regard to atopic dermatitis (AD) development and, especially, severity. Our aim here was to test if such interaction can be detected on the genetic level. The combined effect of the TLR2 gene (TLR2) rs4696480 and the FcεRI α-chain gene (FCER1A) rs2252226 and rs2251746 polymorphisms on the AD severity as measured by SCORAD was assessed. The FCER1A rs2252226 and TLR2 rs4696480 polymorphisms interacted with regard to SCORAD. Higher SCORAD was observed in patients being the TLR2 rs4696480 major homozygotes and carrying at the same time the FCER1A rs2252226 minor allele, compared to those characterized by (any other of) the remaining combined rs2252226 and rs4696480 genotypes. The observation of the epistatic effect of TLR2 and FCER1A genetic variants on SCORAD is in line with the involvement of the interaction TLRs-FcεRI in the pathophysiology of AD.

Background Prenatal exposure to infections can modify immune development. These environmental disturbances during early life potentially alter the incidence of inflammatory disorders as well as priming of immune responses. Infection with the helminth Schistosoma mansoni is widely studied for its ability to alter immune responsiveness and is associated with variations in coinfection, allergy, and vaccine efficacy in endemic populations. Objective Exposure to maternal schistosomiasis during early life, even without transmission of infection, can result in priming effects on offspring immune responses to bystander antigenic challenges as related to allergic responsiveness and vaccination, with this article seeking to further clarify the effects and underlying immunologic imprinting. Methods Here, we have combined a model of chronic maternal schistosomiasis infection with a thorough analysis of subsequent offspring immune responses to allergy and vaccination models, including viral challenge and steady-state changes to immune cell compartments. Results We have demonstrated that maternal schistosomiasis alters CD4+ responses during allergic sensitization and challenge in a skewed IL-4/B-cell–dominant response to antigenic challenge associated with limited inflammatory response. Beyond that, we have uncovered previously unidentified alterations to CD8+ T-cell responses during immunization that are dependent on vaccine formulation and have functional impact on the efficacy of vaccination against viral infection in a murine hepatitis B virus model. Conclusion In addition to steady-state modifications to CD4+ T-cell polarization and B-cell priming, we have traced these modified CD8+ responses to an altered dendritic cell phenotype sustained into adulthood, providing evidence for complex priming effects imparted by infection via fetomaternal cross talk.

In addition to a well-known immunologic background of atherosclerosis and influences of inflammation on arterial and venous thrombosis, there is growing evidence for the presence of links between allergy and vascular or thrombotic disorders. In this interpretative review, five pretty well-documented areas of such overlap are described and discussed, including: (1) links between atherosclerosis and immunoglobulin E or atopy, (2) mutual effects of blood lipids and allergy, (3) influence of atopy and related disorders on venous thromboembolism, (4) the role of platelets in allergic diseases, and (5) the functions of protein C system in atopic disorders.

Venous thromboembolism (VTE) has been shown to be associated with inflammation. Statins that might reduce VTE risk have been found to exert anti-inflammatory properties in patients at cardiovascular risk. We sought to investigate whether anti-inflammatory effects of atorvastatin can be observed in VTE patients.Atorvastatin 40 mg/d was given for 3 days to 26 consecutive VTE patients following discontinuation of anticoagulant therapy and 25 controls. We evaluated interleukin (IL)-1b, IL-6, IL-8, IL-10, soluble P-selectin and von Willebrand factor (vWF) antigen in peripheral venous blood.The VTE patients displayed higher C-reactive protein (p=0.013), IL-1b (p=0.03), IL-8 (p=0.03) and vWF (p0.0001) compared with the controls. In VTE patients atorvastatin decreased IL-6 (p=0.0003), IL-8 (p=0.003) and P-selectin (p0.0001), but increased IL-10 (p=0.001), with no association with C-reactive protein or cholesterol-lowering effects. Atorvastatin reduced IL-1b (p=0.01), IL-6 (p=0.03) and P-selectin (p=0.002) in controls. Residual venous thrombosis was associated with elevated IL-6 and P-selectin, whereas patients with proximal deep vein thrombosis showed elevated P-selecitn prior to and following statin administration (all p0.05).A 3-day administration of atorvastatin reduces inflammation without decrease in C-reactive protein in VTE patients.

We identified a male Polish patient with a very rare minor homozygous GG genotype of the tissue factor (TF) +5466A>G polymorphism, who within two months experienced a transient ischemic attack (TIA) and ischemic stroke of unknown origin associated with the presence of patent foramen ovale below 40 years of age. A relationship between the TF +5466GG genotype and cerebrovascular thromboembolic events could be explained by detectable coagulant TF activity determined in a clotting assay and increased immunoreactive TF levels detected in plasma 5 years after the previous TIA and stroke. Given the role of TF-induced pathway in blood coagulation, it might be speculated that the TF +5466A>G polymorphism, especially in the homozygous GG form, predisposes to increased risk of cerebrovascular ischemic events. There is a need to conduct a prospective study on the effect of TF +5466A>G polymorphism on the risk of cryptogenic stroke.

There is growing evidence that the 174 G/C interleukin-6 (IL-6) gene promoter polymorphism is associated with various manifestations of atherosclerosis [1–3]. This polymorphism has also been reported to affect levels of circulating IL-6 [1,2], which interplays with several markers of inflammation and haemostatic factors [4], and is involved in the pathogenesis of cardiovascular disease [1,2,4]. Statins and angiotensin-converting enzyme (ACE) inhibitors exert several, so-called pleiotropic effects, including antiinflammatory, antithrombotic and profibrinolytic properties [5,6]. Recently, the combined therapy with a statin and an ACE inhibitor has been found to exert additive effects on systemic cardiovascular risk markers (among others IL-6) in mice [7]. Therefore, we decided to analyze a possible association between the 174 G/C IL-6 gene polymorphism and antiinflammatory and antithrombotic effects of combined therapy with a statin and ACE inhibitor in patients with coronary heart disease (CHD). We recruited 24 men (aged 57.7T1.7 years) with CHD, otherwise healthy, not taking ACE inhibitors or statins for at least 42 days before enrollment. Atorvastatin (40 mg/d) and quinapril (10 mg/d) were administered to all the patients for 56 consecutive days. Each patient did not take any other medication during the study (except for low-dose aspirin and h-blocker at the unchanged dosage). The patients provided written informed consent and the study was approved by the University Ethics Committee. Genotyping for the 174 G/C IL-6 polymorphism was performed by the polymerase chain reaction (forward primer