Chronic alcoholism causes deleterious conditioning of innate immunity.
OBJECTIVE
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 (TNFalpha, IL1beta, 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 IL1beta-, but reduced TNFalpha- and IL12-production (P = 0.004, P = 0.0042 and P = 0.001, respectively). While IL1- and TNFalpha-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.
Department of Immunology, Medical Faculty, University of Greifswald, Greifswald, Germany. frankj@uni-greifswald.de
Johannes
J
Frank
Karin
K
Witte
Wieland
W
Schrödl
Christine
C
Schütt
D000437:Alcoholism / Q000276:immunology* / Q000503:physiopathology* / Q000628:therapy; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D002352:Carrier Proteins / Q000096:biosynthesis; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000009:adverse effects; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D007447:Invertebrate Hormones / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D008297:Male; D010808:Physical Examination; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000209:etiology; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D002352:Carrier Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007378:Interleukins; D007447:Invertebrate Hormones; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; C042866:antilipopolysaccharide antibodies; C034705:antilipopolysaccharide factor (Limulus); D000431:Ethanol