Author: Alex Thompson

Alcohols Effects on Lung Health and Immunity Alcohol Research: Current Reviews

Alcohol-induced failure of the mucociliary system could interfere with the clearance of pathogens from the airways and thereby may contribute to the increased risk of pulmonary infections in people with chronic heavy alcohol use (Sisson 2007). In addition to neutrophil recruitment to infected areas and reduced neutrophil-killing potential, production of these cells also is affected. In healthy individuals, the bone marrow produces approximately 120 billion neutrophils per day (Cartwright et al. 1964; von Vietinghoff and Ley 2008). Moreover, bone-marrow neutrophil production is significantly increased 24 to 48 hours after a systemic bacterial infection (Melvan et al. 2011). Alcohol exposure suppresses neutrophil production by the bone marrow and other blood cell–producing (i.e., hematopoietic) tissues (Melvan et al. 2011; Raasch et al. 2010; Siggins et al. 2011). This decreased neutrophil proliferation may account for the decreased number of neutrophils found in the lungs during the host response to pneumonia following alcohol consumption.

  1. Although these risks of alcohol consumption on the lung are well described, mechanisms by which alcohol abuse promotes acute lung injury are poorly understood.
  2. While alcoholism has many well-known medical consequences such as liver injury and pancreatitis, the effects of chronic alcohol exposure on the respiratory system are often overlooked.
  3. Interestingly, human studies have also confirmed that there is decreased cell surface expression of the GM-CSF receptor in alveolar macrophages from alcoholics compared to non-alcoholics (17).
  4. Thus, some studies indicate that alcohol has no effect on neutrophil phagocytosis or pathogen killing (Nilsson et al. 1996; Spagnuolo and MacGregor 1975), whereas other studies demonstrate that acute alcohol exposure impairs functional activities of neutrophils.

Types of T Cells

Another potential therapeutic target is Nrf2, which can be activated by plant-derived compounds (i.e., phytochemicals), such as sulforaphane (Hybertson et al. 2011; Jensen et al. 2013). One clinical study (Burnham et al. 2012) evaluating the effects of 7-day treatment with the Nrf2 activator Protandim® in patients with AUD did not identify any significant improvement in glutathione levels or epithelial function. However, it is possible that combination therapy with an Nrf2 activator plus zinc and/or SAMe may be more effective than zinc and/or SAMe alone, and clinical trials in the near future hopefully will be able to answer that question. It can interfere with the immune system that keeps the lungs healthy and able to fight off infections. However, people with weakened immune systems, such as those who have misused alcohol for a long time, are at increased risk of developing severe and potentially life threatening symptoms.

This protein is a master transcription factor that binds to the antioxidant response element (ARE) in the regulatory (i.e., promoter) region of hundreds of antioxidant and immune-response genes (Jensen et al. 2013). Interestingly, alveolar cells from ethanol-fed rats had increased expression of sodium channels in the membrane facing the interior of the alveoli (i.e., the apical membrane). However, these alcohol-fed rats had diminished airway clearance when challenged with saline, even in the absence of an inflammatory challenge (Guidot et al. 2000). These data suggest that the alveolar epithelium actually is dysfunctional after alcohol exposure, even though it seems normal and is able to regulate the normal air–liquid interface by enhancing sodium channels at the apical surface. In the presence of an inflammatory reaction, the compensatory mechanism likely becomes overwhelmed, resulting in greater susceptibility to barrier disruption and flooding of the alveolar space with protein-containing flu.

What Are the Effects of Alcohol on the Body?

However, many patients with AUD seek care for their addiction precisely because they are motivated to become or remain healthy and, consequently, are likely to adhere to their treatment regimen. Even if patients seeking treatment for AUD have equally low adherence rates, tens of thousands of individuals could benefit from these relatively simple and inexpensive treatments every year in the United States alone. Researchers and clinicians are just beginning to scratch the surface of this challenging problem, but the rapid pace of experimental and clinical research in the past two decades offers hope that in the relatively near future the devastating effects of AUD on lung health can be ameliorated. Chronic + binge ethanol feeding is known to cause immune cell infiltration in the liver, predominantly characterized by neutrophil accumulation. Therefore, markers of macrophages (F4/80 and Cd68) and neutrophils (Ly6g) were measured in liver tissue 9 h and 24 h post-binge using qRT-PCR (Figure 1C).

Alcohol and Acute Lung Injury

Acute lung injury involves the rapid development of noncardiogenic pulmonary edema, and patients with impaired alveolar epithelial fluid clearance are three times more likely to die from ARDS than patients with a maximal ability to clear lung fluid (Ware and Matthay 2001). Although the fluid balance in the lungs is regulated by the concerted actions of both epithelial and endothelial barriers (Mehta et al. 2004), it is the alveolar epithelium which primarily prevents protein and fluid flow into airspaces (Mutlu and Sznajder 2005). A pathological hallmark of ARDS is heterogeneous damage of the alveolar epithelium, with complete loss of the epithelial surface in some areas, whereas other alveoli remain relatively intact.

Sexual and reproductive health

Alcohol-related lung disease (ARLD) is the medical term for lung damage that develops in response to excessive alcohol consumption. This damage may result from various lung conditions, such as viral infections, pneumonia, and acute lung injury. Because of the key role of G-CSF in neutrophil regulation, investigators have hypothesized that alcohol-induced neutrophil dysfunction can be prevented by pretreatment with G-CSF (Nelson et al. 1991). Pneumoniae infection increased neutrophil recruitment compared with that of control animals not receiving G-CSF. In addition to increased neutrophil recruitment, the pre-treated animals also exhibited improved bacterial killing and decreased mortality (Nelson et al. 1991). The findings indicate that G-CSF can prevent alcohol-induced deficits in neutrophil-dependent pulmonary defenses by increasing neutrophil production and bacterial killing function.

What are the symptoms of alcohol-related lung disease?

These and other changes in alveolar epithelial cells predispose people with AUD to developing acute respiratory distress syndrome (ARDS) that is characterized by pulmonary edema. Alcohol exposure has important consequences throughout the entire respiratory system, spanning from the oropharynx to the lung parenchyma, which are outlined in Figure 1. Clinical studies show that alcoholics have a much higher incidence of severe pneumonia caused by more virulent gram-negative organisms (12, 13), and many of these observations can be explained by changes that occur in the upper airway. Most clinical practitioners can attest to the fact that alcoholics have very poor oral hygiene.

Immune system

Even though the most widely recognized target organ damage is alcohol-related liver dysfunction, overall there are roughly 60 types of diseases and injuries that have been linked to alcohol use (6). Other commonly recognized targets of alcoholism include the central nervous system, the heart, and the pancreas, all of which contribute to significant morbidity and mortality for the individual. The exact mechanism by which ethanol caused an apparent increase to central airway resistance (see Figures 5–6) in response to methacholine is unclear. The fact that ethanol exposure under these conditions did not affect basal indices of airway mechanics (Figure 4) speaks against potential physical causes of increase airway resistance, such as loss of tethering, edema and/or septal wall thickening (Bates, 2016).

Recently, a new model of acute-on-chronic alcohol exposure was developed to study alcohol-induced liver disease (Bertola et al., 2013), in which chronic dietary exposure is followed by an acute bolus gavage of alcohol. It is hypothesized that this model better recapitulates the drinking patterns of an individual with an alcohol use disorder. Importantly, hepatic pathology in this acute-on-chronic, or “chronic + binge” model is more similar to human alcoholic liver disease. The impact of such an alcohol exposure regimen on lung architecture and function is not known. The experimental evidence that alcohol can cause a profound defect in the physical barrier of the alveolar epithelium led to the question of why alcohol abuse alone, in the absence of an acute stress such as sepsis, does not cause pulmonary edema.

GM-CSF is secreted by type II alveolar cells and is required for terminal differentiation of circulating monocytes into mature, functional alveolar macrophages (Joshi et al. 2006). Conversely, overexpression of GM-CSF in genetically modified (i.e., transgenic) mice causes increased lung size, excessive growth (i.e., hyperplasia) of alveolar epithelial cells, and improved surfactant protein removal from the alveolar space (Ikegami et al. 1997). Other studies using a rat model of chronic alcohol consumption found that although the levels of GM-CSF in the alveolar space were not affected by alcohol exposure, the expression of GM-CSF receptors was significantly decreased in the membranes of alveolar macrophages (Joshi et al. 2005). Chronic alcohol intake also decreased alveolar binding of PU.1, a transcription factor responsible for GM-CSF activation. When the animals were treated with recombinant GM-CSF, alveolar macrophage bacterial phagocytic capacity, GM-CSF receptor expression, and PU.1 nuclear binding were restored (Joshi et al. 2005). These studies offer the groundwork for understanding the importance of GM-CSF within the lung for the maturation and host immune function of the alveolar macrophage as well as the deleterious impact of chronic alcohol use on these processes.

Over time, this can start to affect the lungs, making the body more vulnerable to lung infections and damage. Glucocorticoids are often used for managing chronic lung conditions, while antibiotics are used to treat bacterial lung infections. You may not experience the therapeutic effects of these medications when you drink alcohol within a few days of your medication dose. T cells are an important part of the immune system and fulfill a variety of functions in defending the organism against various pathogens. To do this, T cells are divided into different subgroups that all have specific functions.