Skin Immunization Obviates Alcohol-Related Immune Dysfunction

Abstract

Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH)-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD) and liver-sparing Meadows-Cook (MC) diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA) by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM), directly to liver (hydrodynamic), or cutaneously (biolistic, ID). We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg), and myeloid-derived suppressor cell (MDSC) populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH), antigen-specific cytotoxic T lymphocyte (CTL), and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects.

Chronic Alcohol Consumption Exacerbates the Severity of Psoriasiform Dermatitis in Mice

“…We further explored whether the minimal skin inflammation of the EtOH VAS mice is a consequence of the direct interaction of EtOH with keratinocytes, as C57BL/6 mice fed alcohol for several weeks have an EtOH concentration in the skin ranging from 5 to 12% of their blood concentrations (Brand et al, 2015). Consistent with a 0.19 g/l blood alcohol concentration in our model (Gäbele et al, 2011), we cultured normal murine epidermal keratinocytes in media containing EtOH at a concentration of 0.02 g/l (the expected EtOH concentration in the skin) or 0.002 g/l.…”

Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment

“…Brand et al [ 25 ] contributed to this Special Issue with the hypotheses that the skin immune network may be relatively preserved in alcohol consumers and proposed that the development of skin-targeted immunizations could circumvent the immune inhibitory effects of alcohol consumption. The authors demonstrate that independent of the feeding model, ethanol ingestion inhibits delayed type hypersensitivity, lysis by cytotoxic T-lymphocytes, and antigen-specific total IgG induced by traditional systemic vaccines.…”

“…The list of articles published in Special Issue “Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment” is presented in Refs. [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”