Flow Cytometric and Immunohistochemical Evaluation of Ethanol‐Induced Changes in Splenic and Thymic Lymphoid Cell Populations

Abstract

Ethanol-induced alterations in the immune system are thought to play a major role in increasing the susceptibility of alcoholics to infections and tumors. One important change in the immune system is the noted loss of lymphoid cells from the thymus and spleen. To examine these alterations we used a model system where C57Bl/6 mice were pair-fed either a Leiber-DeCarli diet containing 7% (v/v) ethanol or an isocaloric control diet. Mice receiving ETOH for 7 days showed a loss of cells from the spleen and thymus; this loss was even more severe after withdrawal for 1 day. The most profound changes were seen after 2 weeks of ETOH. Spleen and thymus cell numbers were reduced to 36% and 6.2%, respectively compared to control mice. Staining of thymocytes with monoclonal antibodies to lymphocyte surface markers and evaluation with flow cytometry revealed that immature thymocytes (PNA+, CD4+/CD8+) were most reduced. Mature thymocytes (CD4+/CD8- or CD4-/CD8+) were depleted, and the CD4+ to CD8+ ratio was increased. Sections of thymus stained with hematoxylin and eosin or with immunohistochemical methods showed atrophy and lymphoid cell depletion. No cortex was histologically identifiable after 2 weeks of ETOH. The spleen cells most affected by ETOH were the B cells. They were reduced to 8.2 x 10(6) cells/spleen (31.5% of the lymphocytes), as compared to 38.5 x 10(6) cells/spleen (50.3% of the lymphocytes) in the control mice. The spleen was atrophic, but the immunoarchitecture was preserved. Ethanol causes a depletion of lymphocytes from the spleen and thymus with alterations in lymphocyte subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol inhibits methionine adenosyltransferase II activity and S-adenosylmethionine biosynthesis and enhances caspase-3-dependent cell death in T lymphocytes: relevance to alcohol-induced immunosuppression

“…Chronic alcohol administration in experimental animal systems leads to a decrease in the absolute numbers of CD4 + T lymphocytes from the periphery and the spleen as well as a reduction in their immune function (6)(7)(8)(9)(10)(11)(12).…”

Sodium Methyldithiocarbamate Causes Thymic Atrophy by an Indirect Mechanism of Corticosterone Up-Regulation

“…Thymic atrophy had been commonly linked to increases in serum corticosterone. Several models of thymic atrophy including chemical exposures (ethanol, propanil, and morphine) and neurogenic/psychogenic stress (restraint stress) indicated that stress-induced increases in serum corticosterone caused thymic atrophy (Saad and Jerrells, 1991;Freier and Fuchs, 1993;Zhao et al, 1995;Tarcic et al, 1998). Further, this increase in corticosterone could be linked to the depletion in DP thymocytes.…”

Effects of ethanol consumption and withdrawal on B cell subpopulations in murine bone marrow

“…In the thymus, immature thymocytes are depleted predominantly, but mature cells are also depleted [14]. Although both T and B cells are lost from the spleen after 7 days of ETOH consumption, B cells are depleted to the greater extent [14].…”

“…In the thymus, immature thymocytes are depleted predominantly, but mature cells are also depleted [14]. Although both T and B cells are lost from the spleen after 7 days of ETOH consumption, B cells are depleted to the greater extent [14]. The cellularity of the spleen returns to normal levels by day 7 after animals are fed laboratory chow diet, rather than ETOH diet [11].…”