Chronic alcohol consumption in mice increases the proportion of peripheral memory T cells by homeostatic proliferation

Zhang, Hui; Meadows, Gary G.

doi:10.1189/jlb.0605317

Cited by 60 publications

(80 citation statements)

References 64 publications

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“…Chronic ethanol consumption is linked to a number of abnormalities of the immune system, including lymphopenia, and downregulation of certain costimulatory molecules on the T cell surface (20), as well as to decreased interaction between leukocytes and endothelial cells (21). Chronic ethanol abuse will typically lead to severe medical consequences, but the potential of beneficial consequences of moderate alcohol intake have been discussed for decades, e.g., with respect to the epidemiology of cardiovascular diseases (22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Ethanol prevents development of destructive arthritis

Jonsson

Verdrengh

Brisslert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Environmental factors are thought to play a major role in the development of rheumatoid arthritis. Because the use of ethanol is widespread, we assessed the role of ethanol intake on the propensity to develop chronic arthritis. Collagen type II-immunized mice were given water or water containing 10% (vol/vol) ethanol or its metabolite acetaldehyde. Their development of arthritis was assessed, as well as the impact of ethanol on leukocyte migration and activation of intracellular transcription factors. Mice exposed daily to this dose of ethanol did not display any liver toxicity, and the development of erosive arthritis was almost totally abrogated. In contrast, the antibody-mediated effector phase of collageninduced arthritis was not influenced by ethanol exposure. Also, the major ethanol metabolite, acetaldehyde, prevented the development of arthritis. This antiinflammatory and antidestructive property of ethanol was mediated by (i) down-regulation of leukocyte migration and (ii) up-regulation of testosterone secretion, with the latter leading to decreased NF-B activation. We conclude that low but persistent ethanol consumption delays the onset and halts the progression of collagen-induced arthritis by interaction with innate immune responsiveness.inflammation ͉ cytokines ͉ sex hormones ͉ antibodies ͉ immunity E xcessive alcohol consumption depresses the immune system and increases the propensity to severe bacterial infections, including pneumonia (1), tuberculosis (2), and bacterial peritonitis (3), and to viral infections (4-6). However, some epidemiological studies have suggested that light to moderate ethanol consumption has protective effects against several diseases including chronic heart diseases (7, 8) and ischemic stroke (9).Ethanol consumption has also been implicated in the pathogenesis of systemic lupus erythematosus (SLE), a complex autoimmune disease in the development of which environmental and genetic factors interact. Indeed, some investigators have found that exposure to ethanol is associated with a lower risk for developing SLE (10, 11), whereas others did not observe any effect of alcohol consumption on the incidence of SLE (12, 13). The association between ethanol and rheumatoid arthritis (RA) has been discussed in some studies, but definite conclusions could not be drawn (14-16). Studies so far have been of an epidemiological nature and therefore have not provided any hints about the biological mechanisms of environmental stimuli in the development of autoimmune disease. Our aim here was to assess whether low but persistent consumption of ethanol in quantities nontoxic to liver might affect the incidence and disease manifestation of collagen type II (CII)-induced arthritis (CIA), an established model of human RA. Our results suggest that ethanol intake delays the onset and halts the progression of destructive arthritis. Results Effect of Ethanol Consumption on Development of CIA.To assess whether ethanol drinking has any impact on the development of CIA, CII-immunized mice were provided w...

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Section: Discussionmentioning

confidence: 99%

Ethanol prevents development of destructive arthritis

Jonsson

Verdrengh

Brisslert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…It is well known that chronic alcohol consumption affects the immune system [20]. A large body of data indicates that chronic alcohol consumption in humans and mice activates the immune system, which is reflected in the activation of CD8 + T cells, dendritic cells (DC), and NKT cells, and increased production of pro-inflammatory cytokines such as IFN-γ and TNF-α [21-25]. We found that chronic alcohol consumption along with advancing growth of s.c. melanoma leads to inhibition in the expansion of memory and melanoma-specific CD8 + T cells, acceleration in the decay of Th1 cytokine producing CD8 + T cells [26], and compromised circulation of mature B cells [27].…”

Section: Introductionmentioning

confidence: 99%

Chronic alcohol consumption inhibits melanoma growth but decreases the survival of mice immunized with tumor cell lysate and boosted with α-galactosylceramide

Zhang

Zhu

Meadows

et al. 2015

International Immunopharmacology

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Alcohol consumption increases the incidence of multiple types of cancer. However, how chronic alcohol consumption affects tumor progression and host survival remains largely unexplored. Using a mouse B16BL6 melanoma model, we studied the effects of chronic alcohol consumption on s.c. tumor growth, iNKT cell antitumor immune response, and host survival. The results indicate that although chronic alcohol consumption inhibits melanoma growth, this does not translate into increased host survival. Immunizing mice with a melanoma cell lysate does not significantly increase the median survival of water-drinking, melanoma-bearing mice, but significantly increases the median survival of alcohol-consuming, melanoma-bearing mice. Even though survival is extended in the alcohol-consuming mice after immunization, the mean survival is not different from the immunized mice in the water-drinking group. Immunization with tumor cell lysate combined with α-galatosylceramide activation of iNKT cells significantly increases host survival of both groups of melanoma-bearing mice compared to their respective non-immunized counterparts; however, the median survival of the alcohol-consuming group is significantly lower than that of the water-drinking group. Alcohol consumption increases NKT cells in the thymus and blood and skews NKT cell cytokine profile from Th1 dominant to Th2 dominant in the tumor-bearing mice. In summary, these results indicate that chronic alcohol consumption activates the immune system, which leads to the inhibition of s.c. melanoma growth and enhances the immune response to immunization with melanoma lysate. With tumor progression, alcohol consumption accelerates iNKT cell dysfunction and compromises antitumor immunity, which leads to decreased survival of melanoma-bearing mice.

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“…We and others found that chronic alcohol consumption in the steady state increases the percentage of CD8 + T cells exhibiting the memory phenotype and also CD8 + T cells producing IFN-γ [ 31 , 33 ]. We further showed that chronic alcohol consumption increases memory T cells in the steady state through the induction of T cell homeostatic proliferation [ 33 ]. These increased memory and IFN-γ-producing CD8 + T cells in alcohol-consuming mice could play an important protective role in the antitumor immune response.…”

Section: Chronic Alcohol Consumption Inhibits B16bl6 Melanoma Lung Mementioning

confidence: 91%

“…The second is an antitumor function through presentation of antigen to T cells to enhance T cell activation and cytokine production. We found that in the steady state chronic alcohol consumption does not signifi cantly affect the B cell phenotype and nor their distribution in blood and lymph nodes; however, B cell numbers decrease in the spleen [ 33 ]. In melanoma-bearing mice B cells decrease around fourfold in the blood of alcoholconsuming mice with prolonged tumor growth compared to their water-drinking counterparts [ 70 ].…”

Section: Effects Of Chronic Alcohol Consumption On B Cellsmentioning

confidence: 95%

Alcohol Consumption and Antitumor Immunity: Dynamic Changes from Activation to Accelerated Deterioration of the Immune System

Zhang

Zhu

Zhang

et al. 2014

Advances in Experimental Medicine and Biology

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The molecular mechanisms of how alcohol and its metabolites induce cancer have been studied extensively. However, the mechanisms whereby chronic alcohol consumption affects antitumor immunity and host survival have largely been unexplored. We studied the effects of chronic alcohol consumption on the immune system and antitumor immunity in mice inoculated with B16BL6 melanoma and found that alcohol consumption activates the immune system leading to an increase in the proportion of IFN-γ-producing NK, NKT, and T cells in mice not injected with tumors. One outcome associated with enhanced IFN-γ activation is inhibition of melanoma lung metastasis. However, the anti-metastatic effects do not translate into increased survival of mice bearing subcutaneous tumors. Continued growth of the subcutaneous tumors and alcohol consumption accelerates the deterioration of the immune system, which is reflected in the following: (1) inhibition in the expansion of memory CD8+ T cells, (2) accelerated decay of Th1 cytokine-producing cells, (3) increased myeloid-derived suppressor cells, (4) compromised circulation of B cells and T cells, and (5) increased NKT cells that exhibit an IL-4 dominant cytokine profile, which is inhibitory to antitumor immunity. Taken together, the dynamic effects of alcohol consumption on antitumor immunity are in two opposing phases: the first phase associated with immune stimulation is tumor inhibitory and the second phase resulting from the interaction between the effects of alcohol and the tumor leads to immune inhibition and resultant tumor progression.

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Chronic alcohol consumption in mice increases the proportion of peripheral memory T cells by homeostatic proliferation

Cited by 60 publications

References 64 publications

Ethanol prevents development of destructive arthritis

Ethanol prevents development of destructive arthritis

Chronic alcohol consumption inhibits melanoma growth but decreases the survival of mice immunized with tumor cell lysate and boosted with α-galactosylceramide

Alcohol Consumption and Antitumor Immunity: Dynamic Changes from Activation to Accelerated Deterioration of the Immune System

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