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  • 1
    Online Resource
    Online Resource
    Acute alcohol consumption increases systemic endotoxin bioactivity for days in healthy volunteers—with reduced intestinal barrier loss in female
    Springer Science and Business Media LLC ; 2022
    In:  European Journal of Trauma and Emergency Surgery Vol. 48, No. 3 ( 2022-06), p. 1569-1577
    Details
    In: European Journal of Trauma and Emergency Surgery, Springer Science and Business Media LLC, Vol. 48, No. 3 ( 2022-06), p. 1569-1577
    Abstract: Trauma is the most common cause of death among young adults. Alcohol intoxication plays a significant role as a cause of accidents and as a potent immunomodulator of the post-traumatic response to tissue injury. Polytraumatized patients are frequently at risk to developing infectious complications, which may be aggravated by alcohol-induced immunosuppression. Systemic levels of integral proteins of the gastrointestinal tract such as syndecan-1 or intestinal fatty acid binding proteins (FABP-I) reflect the intestinal barrier function. The exact impact of acute alcohol intoxication on the barrier function and endotoxin bioactivity have not been clarified yet. Methods 22 healthy volunteers received a precisely defined amount of alcohol (whiskey–cola) every 20 min over a period of 4 h to reach the calculated blood alcohol concentration (BAC) of 1‰. Blood samples were taken before alcohol drinking as a control, and after 2, 4, 6, 24 and 48 h after beginning with alcohol consumption. In addition, urine samples were collected. Intestinal permeability was determined by serum and urine values of FABP-I, syndecan-1, and soluble (s)CD14 as a marker for the endotoxin translocation via the intestinal barrier by ELISA. BAC was determined. Results Systemic FABP-I was significantly reduced 2 h after the onset of alcohol drinking, and remained decreased after 4 h. However, at 6 h, FABP-I significantly elevated compared to previous measurements as well as to controls ( p   〈  0.05). Systemic sCD14 was significantly elevated after 6, 24 and 48 h after the onset of alcohol consumption ( p   〈  0.05). Systemic FABP-I at 2 h after drinking significantly correlated with the sCD14 concentration after 24 h indicating an enhanced systemic LPS bioactivity. Women showed significantly lower levels of syndecan-1 in serum and urine and urine for all time points until 6 h and lower FABP-I in the serum after 2 h. Conclusions Even relative low amounts of alcohol affect the immune system of healthy volunteers, although these changes appear minor in women. A potential damage to the intestinal barrier and presumed enhanced systemic endotoxin bioactivity after acute alcohol consumption is proposed, which represents a continuous immunological challenge for the organism and should be considered for the following days after drinking.
    Type of Medium: Online Resource
    ISSN: 1863-9933 , 1863-9941
    URL: Article
    DOI: 10.1007/s00068-021-01666-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2276432-X
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  • 2
    Online Resource
    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-5-18)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-5-18)
    Abstract: Excessive alcohol intake is associated with adverse immune response-related effects, however, acute and chronic abuse differently modulate monocyte activation. In this study, we have evaluated the phenotypic and functional changes of monocytes in acutely intoxicated healthy volunteers (HV). Methods Twenty-two HV consumed individually adjusted amounts of alcoholic beverages until reaching a blood alcohol level of 1‰ after 4h (T4). Peripheral blood was withdrawn before and 2h (T2), 4h (T4), 6h (T6), 24h (T24), and 48h (T48) after starting the experiment and stained for CD14, CD16 and TLR4. CD14 bright CD16 - , CD14 bright CD16 + and CD14 dim CD16 + monocyte subsets and their TLR4 expression were analyzed by flow cytometry. Inflammasome activation via caspase-1 in CD14 + monocytes was measured upon an ex vivo in vitro LPS stimulation. Systemic IL-1β and adhesion capacity of isolated CD14 + monocytes upon LPS stimulation were evaluated. Results The percentage of CD14 + monocyte did not change following alcohol intoxication, whereas CD14 bright CD16 - monocyte subset significantly increased at T2 and T24, CD14 bright CD16 + at T2, T4 and T6 and CD14 dim CD16 + at T4 and T6. The relative fraction of TLR4 expressing CD14 + monocytes as well as the density of TLR4 surface presentation increased at T2 and decreased at T48 significantly. TLR4 + CD14 + monocytes were significantly enhanced in all subsets at T2. TLR4 expression significantly decreased in CD14 bright CD16 - at T48, in CD14 bright CD16 + at T24 and T48, increased in CD14 dim CD16 + at T2. IL-1β release upon LPS stimulation decreased at T48, correlating with TLR4 receptor expression. Alcohol downregulated inflammasome activation following ex vivo in vitro stimulation with LPS between T2 and T48 vs . T0. The adhesion capacity of CD14 + monocytes decreased from T2 with significance at T4, T6 and T48. Following LPS administration, a significant reduction of adhesion was observed at T4 and T6. Conclusions Alcohol intoxication immediately redistributes monocyte subsets toward the pro-inflammatory phenotype with their subsequent differentiation into the anti-inflammatory phenotype. This is paralleled by a significant functional depression, suggesting an alcohol-induced time-dependent hyporesponsiveness of monocytes to pathogenic triggers.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.652488
    DOI: 10.3389/fimmu.2021.652488.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 3
    Online Resource
    Online Resource
    Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury
    Hindawi Limited ; 2021
    In:  Journal of Immunology Research Vol. 2021 ( 2021-1-28), p. 1-14
    Details
    In: Journal of Immunology Research, Hindawi Limited, Vol. 2021 ( 2021-1-28), p. 1-14
    Abstract: Background. Recently, identification of immunosuppressive polymorphonuclear leukocytes (PMNL) that were traditionally described as proinflammatory cells emerged in the field of posttraumatic immunity. To understand their local and remote distribution after trauma, PMNL-subsets and the impact of immunomodulatory Club Cell protein (CC)16 that correlates with pulmonary complications were assessed. Methods. C57BL/6N mice were divided into three groups, receiving isolated blunt chest trauma (TxT), undergoing TxT followed by cecal ligation and puncture (CLP, TxT + CLP ) after 24 h, or sham undergoing analgosedation ( n = 18 /group). Further, each group was subdivided into three groups receiving either no treatment (ctrl) or intratracheal neutralization of CC16 by application of anti-CC16-antibody or application of an unspecific IgG control antibody ( n = 6 /group). Treatment was set at the time point after TxT. Analyses followed 6 h post-CLP. PMNL were characterized via expression of CD11b, CD16, CD45, CD62L, and Ly6G by flow cytometry in bone marrow (BM), blood, spleen, lung, liver, and bronchoalveolar and peritoneal lavage fluid (BALF and PL). Apoptosis was assessed by activated (cleaved) caspase-3. Results from untreated ctrl and IgG-treated mice were statistically comparable between all corresponding sham, TxT, and TxT + CLP groups. Results. Immature (CD16dimCD62Lbright) PMNL increased significantly in BM, circulation, and spleen after TxT vs. sham and were significantly attenuated in the lungs, BALF, PL, and liver. Classical-shaped (CD16brightCD62Lbright) PMNL increased after TxT vs. sham in peripheral tissue and were significantly attenuated in circulation, proposing a trauma-induced migration of mature or peripheral differentiation of circulating immature PMNL. Immunosuppressive (CD16brightCD62Ldim) PMNL decreased significantly in the lungs and spleen, while they systemically increased after TxT vs. sham. CLP in the TxT + CLP group reduced immunosuppressive PMNL in PL and increased their circulatory rate vs. isolated TxT, showing local reduction in affected tissue and their increase in nonaffected tissue. CC16 neutralization enhanced the fraction of immunosuppressive PMNL following TxT vs. sham and decreased caspase-3 in the lungs post-CLP in the TxT + CLP group, while apoptotic cells in the liver diminished post-TxT. Posttraumatic CC16 neutralization promotes the subset of immunosuppressive PMNL and antagonizes their posttraumatic distribution. Conclusion. Since CC16 affects both the distribution of PMNL subsets and apoptosis in tissues after trauma, it may constitute as a novel target to beneficially shape the posttraumatic tissue microenvironment and homeostasis to improving outcomes.
    Type of Medium: Online Resource
    ISSN: 2314-7156 , 2314-8861
    URL: Article
    DOI: 10.1155/2021/6647753
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2817541-4
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  • 4
    Online Resource
    Online Resource
    Reduced phagocytosis, ROS production and enhanced apoptosis of leukocytes upon alcohol drinking in healthy volunteers
    Springer Science and Business Media LLC ; 2022
    In:  European Journal of Trauma and Emergency Surgery Vol. 48, No. 4 ( 2022-08), p. 2689-2699
    Details
    In: European Journal of Trauma and Emergency Surgery, Springer Science and Business Media LLC, Vol. 48, No. 4 ( 2022-08), p. 2689-2699
    Abstract: Alcohol drinking is associated with a serious risk of developing health problems as well as with a large number of traumatic injuries. Although chronic alcohol misuse is known to contribute to severe inflammatory complications, the effects of an acute alcohol misuse are still unclear. Here, the impact of acute alcohol drinking on leukocyte counts and their cellular functions were studied. Methods Twenty-two healthy volunteers (12 female, 10 male) received a predefined amount of a whiskey-cola mixed drink (40% v/v), at intervals of 20 min, over 4 h to achieve a blood alcohol concentration of 1‰. Blood samples were taken before drinking T 0 , 2 h ( T 2 ), 4 h ( T 4 ), 6 h ( T 6 ), 24 h ( T 24 ) and 48 h ( T 48 ) after starting drinking alcohol. Leukocytes, monocytes and granulocyte counts and their functions regarding the production of reactive oxidative species (ROS), phagocytosis and apoptosis were analyzed by flow cytometry. Results Total leukocyte counts significantly increased at T 2 and T 4 , while granulocyte and monocyte counts decreased at T 4 and T 6 vs. T 0 . Monocytes increased significantly at T 24 and T 48 vs. T 0 . While the total number of ROS-producing leukocytes and notably granulocytes significantly increased, in parallel, the intracellular ROS intensity decreased at T 2 and T 6 . The numbers of ROS-positive monocytes have shown a delayed modulation of ROS, with a significant reduction in the total number of ROS-producing cells at T 48 and a significantly reduced intracellular ROS-intensity at T 24 . Phagocyting capacity of leukocytes significantly decreased at T 4 and T 6 . In general leukocytes, and notably granulocytes demonstrated significantly increased early ( T 2 ), while monocyte exerted significantly increased late apoptosis ( T 24 and T 48 ). Conclusions Alcohol drinking immediately impacts leukocyte functions, while the impact on monocytes occurs at even later time points. Thus, even in young healthy subjects, alcohol drinking induces immunological changes that are associated with diminished functions of innate immune cells that persist for days.
    Type of Medium: Online Resource
    ISSN: 1863-9933 , 1863-9941
    URL: Article
    DOI: 10.1007/s00068-021-01643-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2276432-X
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