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Background: Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (pneumococcus) and influenza vaccines are administered in children to prevent infections caused by these pathogens. The benefits of vaccination for asthma control in children and the elicited immune response are not fully understood. This study aimed to investigate the impact of these vaccinations on respiratory infections, asthma symptoms, asthma severity and control status, pathogen colonization and in vitro immune responses to different stimulants mimicking infections in asthmatic children. Methods: Children aged 4–6 years were recruited into the multicentre prospective PreDicta study conducted across five European countries. Information about vaccination history, infections, antibiotic use, inhaled corticosteroid (ICS) use and asthma symptoms in the last 12 months were obtained from questionnaires of the study. Nasopharyngeal samples were collected at the first visit to assess bacterial and viral colonization, and venous blood for isolation of peripheral blood mononuclear cells (PBMCs). The PBMCs were stimulated with phytohemagglutinin, R848, Poly I:C and zymosan. The levels of 22 cytokines and chemokines were measured in cell culture supernatants using a luminometric multiplex assay. Results: One‐hundred and forty asthmatic preschool children (5.3 ± 0.7 years) and 53 healthy children (5.0 ± 0.8 years) from the PreDicta cohort were included in the current study. Asthmatic children were associated with more frequent upper and lower respiratory infections, and more frequent and longer duration of antibiotic use compared with healthy children. In asthmatic children, sufficient H. influenzae vaccination was associated with a shorter duration of upper respiratory infection (URI) and overall use and average dose of ICS. The airway colonization was characterized by less pneumococcus and more rhinovirus. Pneumococcal vaccination was associated with a reduction in the use rate and average dose of ICS, improved asthma control, and less human enterovirus and more H. influenzae and rhinovirus (RV) airway colonization. Influenza vaccination in the last 12 months was associated with a longer duration of URI, but with a decrease in the occurrence of lower respiratory infection (LRI) and the duration of gastrointestinal (GI) infection and antibiotic use. Asthmatic preschoolers vaccinated with H. influenzae, pneumococcus or influenza presented higher levels of Th1‐, Th2‐, Th17‐ and regulatory T cells (Treg)‐related cytokines in unstimulated PBMCs. Under stimulation, PBMCs from asthmatic preschoolers with pneumococcal vaccination displayed a predominant anti‐inflammatory immune response, whereas PBMCs from asthmatic children with sufficient H. influenzae or influenza vaccination were associated with both pro‐ and anti‐inflammatory immune responses. Conclusion: In asthmatic preschoolers, the standard childhood vaccinations to common respiratory pathogens have beneficial effects on asthma control and may modulate immune responses relevant to asthma pathogenesis. [ABSTRACT FROM AUTHOR]

Atherogenesis is associated with chronic gut infections; however, the mechanisms are not clear. The aim of the study was to determine whether lipopolysaccharide of E. coli (E. coli LPS) may affect endothelial barrier and modify IL‐10 expression in dendritic cells (DCs). Human umbilical vein endothelial cells (HUVECs) and monocyte‐derived DCs were treated with E. coli LPS, apolipoprotein B100 (ApoB100) and 7‐ketocholesterol (7‐kCH) – harmful oxidized form of cholesterol. The effect of E. coli LPS, 7‐kCH and ApoB100 on the barrier functions of HUVECs in real‐time cell electric impedance sensing system (RTCA‐DP) was assessed. Furthermore, the effect of 7‐kCH and ApoB100 on barrier functions of HUVECs co‐cultured with DCs previously treated with LPS was analyzed. Both E. coli LPS and 7‐kCH decreased barrier functions of HUVECs and reduced tight junction protein mRNA expression, whereas ApoB100 increased endothelial barrier. In DCs, ApoB100 and E. coli LPS decreased IL‐10 mRNA expression. In HUVECs co‐cultured with DCs treated with LPS and subsequently pulsed with ApoB100 or 7‐kCH, IL‐10 mRNA expression was lower. E. coli LPS‐exposed DCs diminished the protective effect of ApoB100 on endothelial integrity and led to the decrease in occludin mRNA expression. LPS potentially derived from gut microflora may destabilize endothelial barrier together with oxidized cholesterol and intensify the immunogenicity of ApoB100. [ABSTRACT FROM AUTHOR]

Studies have shown that HMG-CoA reductase inhibitors possess anti-inflammatory properties, for example, decreasing serum levels of proinflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6) or decreasing the activity of numerous effector mechanisms. However, they also may influence the immune system by affecting a wide range of regulatory actions, for example, Treg- and Th2-type response activation as well as Th1 and Th17 response diminishing. These features provide the rationale for potential application of statins in treating chronic inflammatory diseases and other disorders with the involvement of the immune system. This article seeks to review the immunomodulatory actions of statins and their possible implementation in treating rheumatoid arthritis, multiple sclerosis, and other autoimmune disorders in humans.