CHRONIC ALCOHOLISM CAUSES DELETERIOUS CONDITIONING OF INNATE IMMUNITY
Identifieur interne : 000846 ( Main/Exploration ); précédent : 000845; suivant : 000847CHRONIC ALCOHOLISM CAUSES DELETERIOUS CONDITIONING OF INNATE IMMUNITY
Auteurs : Johannes Frank [Allemagne] ; Karin Witte ; Wieland Schro Dl [Allemagne] ; Christine Schu TtSource :
- Alcohol and Alcoholism [ 0735-0414 ] ; 2004-NaN.
Abstract
Aims: To examine the immune consequences of chronic alcoholism in man, in relation to the known association between alcoholism and raised incidence and severity of infections. Methods: In 36 alcoholics without liver disease, at the point of commencing withdrawal from alcohol, the following measures of immune competence were measured: the immunophenotypes of cells, acute phase proteins, the endotoxin-neutralizing capacity (ENC) of the serum, titers of anti-lipopolysaccharide (LPS) antibodies, and ex vivo cytokine inducibility in T cells and monocytes (TNFα, IL1β, IL1RA, IL4, IL6, IL8, IL10 and IL12). The results were compared to those from healthy volunteers (day controls). Measures were repeated after 8–13 days of abstinence. Results: LPS-binding protein (LBP) and soluble CD14 (sCD14) were significantly increased in patients' sera at the outset of withdrawal, whereas reduced titers of anti-LPS IgG (P = 0.012) and a reduced ENC (P = 0.001) were measured. Only ENC rapidly returned to normal values after withdrawal therapy. Cytokine induction with phorbol ester showed no significant alterations in patients' T cells. Patients' monocytes, however, responded to LPS stimulation with enhanced IL1β-, but reduced TNFα- and IL12-production (P = 0.004, P = 0.0042 and P = 0.001, respectively). While IL1- and TNFα-responses normalized after the withdrawal period, impairment of the IL12 response persisted throughout the observation period of 2 weeks. Conclusions: Alcoholism results in a prolonged LPS-mediated hypoinflammatory conditioning of the innate but not the adaptive immune system, which is not reversed immediately after withdrawal. This alcohol-induced status of the immune system predisposes to infections and sepsis by blunting initial response to the pathogens.
Url:
DOI: 10.1093/alcalc/agh083
Affiliations:
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Methods: In 36 alcoholics without liver disease, at the point of commencing withdrawal from alcohol, the following measures of immune competence were measured: the immunophenotypes of cells, acute phase proteins, the endotoxin-neutralizing capacity (ENC) of the serum, titers of anti-lipopolysaccharide (LPS) antibodies, and ex vivo cytokine inducibility in T cells and monocytes (TNFα, IL1β, IL1RA, IL4, IL6, IL8, IL10 and IL12). The results were compared to those from healthy volunteers (day controls). Measures were repeated after 8–13 days of abstinence. Results: LPS-binding protein (LBP) and soluble CD14 (sCD14) were significantly increased in patients' sera at the outset of withdrawal, whereas reduced titers of anti-LPS IgG (P = 0.012) and a reduced ENC (P = 0.001) were measured. Only ENC rapidly returned to normal values after withdrawal therapy. Cytokine induction with phorbol ester showed no significant alterations in patients' T cells. Patients' monocytes, however, responded to LPS stimulation with enhanced IL1β-, but reduced TNFα- and IL12-production (P = 0.004, P = 0.0042 and P = 0.001, respectively). While IL1- and TNFα-responses normalized after the withdrawal period, impairment of the IL12 response persisted throughout the observation period of 2 weeks. Conclusions: Alcoholism results in a prolonged LPS-mediated hypoinflammatory conditioning of the innate but not the adaptive immune system, which is not reversed immediately after withdrawal. This alcohol-induced status of the immune system predisposes to infections and sepsis by blunting initial response to the pathogens.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>District de Leipzig</li><li>Saxe (Land)</li></region><settlement><li>Leipzig</li></settlement></list><tree><noCountry><name sortKey="Schu Tt, Christine" sort="Schu Tt, Christine" uniqKey="Schu Tt C" first="Christine" last="Schu Tt">Christine Schu Tt</name><name sortKey="Witte, Karin" sort="Witte, Karin" uniqKey="Witte K" first="Karin" last="Witte">Karin Witte</name></noCountry><country name="Allemagne"><noRegion><name sortKey="Frank, Johannes" sort="Frank, Johannes" uniqKey="Frank J" first="Johannes" last="Frank">Johannes Frank</name></noRegion><name sortKey="Schro Dl, Wieland" sort="Schro Dl, Wieland" uniqKey="Schro Dl W" first="Wieland" last="Schro Dl">Wieland Schro Dl</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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