A recent perspective on alcohol, immunity, and host defense

Abstract

Background: Multiple line of clinical and experimental evidence demonstrates that both acute, moderate, and chronic, excessive alcohol use result in various abnormalities in the functions of the immune system.

Methods: Medline and PubMed databases were used to identify published reports with particular interest in the period of 2000-2008 in the subject of alcohol use, infection, inflammation, innate, and adaptive immunity.

Results: This review article summarizes recent findings relevant to acute or chronic alcohol use-induced immunomodulation and its consequences on host defense against microbial pathogens and tissue injury. Studies with in vivo and in vitro alcohol administration are both discussed. The effects of alcohol on lung infections, trauma and burn injury, liver, pancreas, and cardiovascular diseases are evaluated with respect to the role of immune cells. Specific changes in innate immune response and abnormalities in adaptive immunity caused by alcohol intake are detailed.

Conclusion: Altered inflammatory cell and adaptive immune responses after alcohol consumption result in increased incidence and poor outcome of infections and other organ-specific immune-mediated effects.

Figure 1. Induction of immune responses by pathogens

Various pathogens, such as bacteria, viruses, fungi and parasites, trigger host defense through activation of an immune response. Pathogens are recognized by pattern recognition receptors including the family of Toll-like receptors (TLRs) (10 different TLRs in humans and 13 in rodents), NOD-LRR proteins, peptidoglycan recognition receptors (PGRP), and RNA helicases expressed on host cells. PRRs trigger various signaling pathways to initiate activation of innate and/or adaptive immune responses. Innate immunity involves recruitment and activation of neutrophil leukocytes, macrophages, monocytes, dendritic cells and natural killer cells to initiate the immune response. These cells also produce immune mediators aimed at inhibition of the pathogen (interferons), recruitment (chemokines) and modulation (cytokines) of other immune cells. The innate immunity is also pivotal in initiation of adaptive immune responses via the antigen presenting function of dendritic cells and other antigen presenting cell types. Pathogen/antigen-specific T cell activation extends to both the CD4+ and CD8+ T lymphocyte populations and the extent of T cell activation and proliferation can be regulated by regulatory T cell subsets, Th17+ T cells and NKT cells. Adaptive immunity also involves activation of B lymphocytes and induction of immunoglobulin switching leading to production of pathogen-specific antibodies. All of these processes of the innate and adaptive immunity work in concert to ultimately achieve pathogen elimination.

Figure 2. Alcohol impairs innate and adaptive immunity

Acute and chronic alcohol has broad immunoregulatory effects. Cells of the innate immune system (macrophages, monocytes, dendritic cells, NK cells) are modulated by alcohol in their capacity to respond to pathogens. Inflammatory cell responses including production of pro-inflammatory cytokines (IL-1, TNFa) and NF-kB activation are inhibited by acute alcohol exposure while chronic alcohol augments these pro-inflammatory responses. The antigen presenting function of both monocytes and dendritic cells is impaired by both acute and chronic alcohol and this contributes to impaired induction of adaptive immune responses. Both acute and chronic alcohol inhibits T cell functions and IL-12 production and results in alterations in Th1 (IFNg) and Th2 (IL-10) cytokine production. These alcohol-induced abnormalities then collectively contribute to impaired pathogen elimination and reduced adaptive immune responses in the alcohol-exposed host.