Depressed delayed cutaneous hypersensitivity in alcoholic hepatitis

Abstract

Delayed cutaneous hypersensitivity was studied in 10 patients with severe alcoholic hepatitis, 9 patients with either inactive alcoholic cirrhosis or alcoholic fatty liver, and 10 agematched controls. The mean response of the alcoholic hepatitis group was significantly less compared to controls for SK-SD (P less than 0.001), mumps (P less than 0.001), trichophyton (P less than 0.025), and Candida albicans (P less than 0.025). Upon clinical recovery, the response of the 6 surviving patients with alcoholic hepatitis was similar to controls for 4 of the 5 antigens tested, and the improvements in response to SK-SD and Candida albicans were significant (P less than 0.02 and P less than 0.05). The mean percentage and absolute numbers of thymus-derived lymphocytes were significantly less in the alcoholic hepatitis group compared with controls. Both the alcoholic hepatitis patients and patients with less advanced alcoholic liver disease had a diminished response to concanavalin A and phytohemagglutinin. This study demonstrates a reversible depression of delayed cutaneous hypersensitivity in alcoholic hepatitis. Several mechanisms may help account for this finding. We recommend that skin tests in patients with alcoholic hepatitis be interpreted with this phenomenon in mind.

The role of alcoholism and liver disease in the appearance of serum antibodies against acetaldehyde adducts

“…The finding that some of our alcoholic patients did not have abnormal or only slightly elevated hemagglutination titers is not explained but could be understood on the basis that a continuous antigen challenge may lead to immune tolerance or, alternatively, that alcohol, when consumed chronically in high doses, may act as an immunosuppressive drug (30). Supportive evidence is provided by the observation that alcoholic individuals have clinical signs of impaired cell-mediated immunity with reduced skin test reactions to a variety of antigens (31)(32)(33). Moreover, a disturbance in the humoral immune response is indicated by reports that ethanol consumption at the time of antigenic challenge can result in a lack of or a poor immune response to an antigen not previously experienced, although a normal anamnestic response to antigens recognized earlier may occur (34)(35)(36).…”

Recent understanding of immunological aspects in alcoholic hepatitis

“…There have been many reports about immunological aspects of ALD, but they have not been consistent, because each report has been a reflection of the immunological experimental procedures available when the investigation was performed. For example, various pathogeneses, such as an antibody against Mallory body [10,11], an antibody against lipopolysaccharide [12], an antibody against self-antigen or alcoholic adducts [13][14][15][16][17], cytotoxic T cells [18][19][20][21], decrease in cellular immunity [22][23][24], IgA [25][26][27], phagocytic activity [28], and cytokines [29][30][31], have been considered as causes for alcoholic hepatitis in a long research history of alcoholic liver diseases [32]. We review the immunological aspects of alcoholic hepatitis in this article.…”

Mechanisms by Which Chronic Ethanol Feeding Limits the Ability of Dendritic Cells to Stimulate T-Cell Proliferation

“…I NCREASED INCIDENCE AND severity of a wide variety of infections have long been observed in chronic alcoholic individuals (Cook, 1998;Lau et al, 2009;MacGregor and Louria, 1997;Szabo, 1999;Zhang et al, 2008). Chronic ethanol (EtOH) exposure impairs T-cell responses to antigenic challenge in both humans and animal models (Chang and Norman, 1999;Geissler et al, 1997;Gluckman et al, 1977;Gurung et al, 2009;Meyerholz et al, 2008;Snyder et al, 1978;Tonnesen et al, 1992). These observed deficiencies are clearly due in part to intrinsic EtOH-induced T-cell defects; however, failure of EtOH-exposed dendritic cells (DCs) to appropriately activate T cells could also play a significant role in suboptimal T-cell function.…”