Long lasting immunological effects of ethanol after withdrawal.
The aim of the present study was to analyze on chronic alcoholic patients the effect of ethanol (EtOH) withdrawal on the immune system through the investigation of the distribution of PB lymphoid subsets, using multiple-stainings with monoclonal antibodies and flow cytometry. For this purpose a group of 20 patients with active alcoholism without liver disease, negative for hepatitis virus, and without malnutrition was analyzed and followed for 9 months after alcohol consumption had been discontinued. Twenty-five age- and sex-matched healthy volunteers were included in the study. The following panel of monoclonal antibodies combinations (FITC/PE/PerCP or PE-Cy5) was used: TCR alpha beta/CD3/HLA DR, CD25/CD56/CD3, TCR gamma delta/CD3/HLA DR, CD45RA/CD45R0/CD4, CD3/CD8, CD19/CD5, and CD3/CD11c. Analysis was performed on at least 1,500 events/tube at flow cytometry using the Lysys II software program. During the alcohol intake period, the most striking findings were a significant (P < 0.05) expansion of the CD8+ T-lymphocyte subset, which coexpresses the activation associated antigens HLA DR and CD11c, as well as a significant increase in both NK-cells (CD3-/CD56+) and the T-cell subset with NK activity coexpressing CD3 and CD56 (P < 0.05 and P < 0.01, respectively). In addition, a decrease in the CD5+ B-cells (P < 0.05), associated with reduced serum gamma-globulin levels, was also observed. During alcohol withdrawal, a rapid decrease towards normal values of activated CD8+/HLA DR+ and CD11c+ T-lymphocytes was observed as well as a normalization of CD19+/CD5+ B-cells and gamma-globulin serum levels; these changes might be directly related to EtOH suppression. Surprisingly, however, new immunological imbalances emerged in spite of the absence of alcohol intake. Thus, a progressive and significant expansion (P < 0.05) of CD4+ T-cells associated with an increased expression of the CD25 activation-related antigen and a preferential use of the CD45R0 isoform by CD4+ T-cells were observed. In parallel, there was an even more evident increase (P < 0.01) in the number of PB NK-cells. Our results show that EtOH consumption induces changes in the immune system, its effects persisting or even becoming more evident after suppression of EtOH intake for a 9 month period.
Laso
F J
FJ
Servicio de Medicina Interna II, Hospital Universitario, Universidad de Salamanca, Spain.
Madruga
J I
JI
San Miguel
J F
JF
Ciudad
J
J
López
A
A
Alvarez Mon
M
M
Orfao
A
A
D000437:Alcoholism / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013375:Substance Withdrawal Syndrome / Q000276:immunology*; D013997:Time Factors
D015703:Antigens, CD; D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000431:Ethanol