Liver and Allergies

Allergies can be a sign of liver problems

Many people experience allergies, but few consider these reactions linked to liver health. By understanding this relationship, steps can be taken to manage allergies and support liver function. Allergies happen when or if the immune system overreacts to substances that are usually harmless, like pollen, dust, or certain foods. However, there is a significant link between liver function and allergic reactions.

The liver is pivotal in detoxifying the body, processing everything from environmental toxins to medications. When the liver is overwhelmed or isn’t working properly, it can result in an accumulation of toxins in the body, triggering or worsening allergic reactions.

Evidence suggests a relevant role for liver and mitochondrial dysfunction in allergic disease. However, the role of hepatic mitochondrial function in food allergy is largely unknown.

Food allergy (FA), defined as an adverse immune response to food proteins, is a major public health issue in Western countries due to its increasing prevalence and severity as well as the negative impact on quality of life and medical care costs. Peanut allergy (PA) is one of the most common types of FA. The prevalence of PA among children in Western countries has doubled in the past 10 years, reaching rates of 1.4–3.0%. In contrast to other FA, such as cow milk allergy, the majority of PA cases persist throughout life and are often associated with life-threatening symptoms. Thus, the investigation of new targets for effective preventive and therapeutic strategies is highly advocated.

Compelling evidence has been recently accumulated that mammals’ mitochondria have multiple critical roles in immunity, and that in addition to being the powerhouse of the cell, they also represent the powerhouse of immunity. In this light, increasing evidence strongly suggests a relevant role for mitochondrial dysfunction, and consequent excessive generation of reactive oxygen species (ROS) in allergy. Mitochondrial dysfunction and elevated ROS have been reported in atopic dermatitis,

allergic rhinitis and asthma. The involvement of liver in FA is emerging. An increased risk for FA in patients affected by severe liver damage has been demonstrated. Studies in a murine model suggest that the liver could act as a source of CD4+ T cells and could play an important role in the IgE response to dietary antigens. Despite the central role played by the liver in the maintenance of immune-metabolic homeostasis being well accepted, the involvement of hepatic mitochondrial function in FA is largely undefined.

An overburdened liver may not only increase mast cell reactions and increased histamine release, higher cholesterol levels and higher liver enzymes in the blood system indicating that the liver is in need of support. It's important to recognize that all liver functions play a role in histamine intolerance.

In addition to being associated with allergic diseases, parasites, bacteria, and venoms, a growing body of research indicates that mast cells and their mediators can regulate liver disease progression. When mast cells are activated, they degranulate and release many mediators, such as histamine, tryptase, chymase, transforming growth factor-β1 (TGF-β1), tumor necrosis factor–α(TNF-α), interleukins cytokines, and other substances that mediate the progression of liver disease. Mast cells are activated in various liver conditions such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, hepatic fibrogenesis, and hepatocellular carcinoma.

Mast cells (MCs) are immune cells of the myeloid lineage that are present in the connective tissue throughout the body and in mucosa tissue. They originate from hematopoietic stem cells in the bone marrow and circulate as MC progenitors in the blood. After migration to various tissues, they differentiate into their mature form, which is characterized by a phenotype containing large granules enriched in a variety of bioactive compounds, including histamine and heparin. These cells can be activated in a receptor-dependent and -independent manner. Particularly, the activation of the high-affinity immunoglobulin E (IgE) receptor, also known as FcεRI, that is expressed on the surface of MCs provoke specific signaling cascades that leads to intracellular calcium influx, activation of different transcription factors, degranulation, and cytokine production. Therefore, MCs modulate many aspects in physiological and pathological conditions, including wound healing, defense against pathogens, immune tolerance, allergy, anaphylaxis, autoimmune defects, inflammation, and infectious and other disorders. In the liver, MCs are mainly associated with connective tissue located in the surrounding of the hepatic arteries, veins, and bile ducts. Recent work has demonstrated a significant increase in MC number during hepatic injury, suggesting an important role of these cells in liver disease and progression.

Mast cells (MCs) are hematopoietic cells of the myeloid lineage. They can be found particularly in tissues with close contact to the environment, such as skin, gastrointestinal tract, upper airways, and lung.

But MCs are also located in other vascularized organs (e.g., liver and kidney). Correlating with their presence in various locations, MCs present as a highly heterogeneous cell population with subtype-dependent differences in cell morphology, histochemical properties, expression of granular proteases, and function, amongst others. This intriguing plasticity and heterogeneity also have their origin in the differentiation process of MCs.

It is more difficult to define what secondary allergies, or better, secondary reactions are.

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Viral infections can also cause so-called secondary allergic reactions. Viruses inhibit the active glucose uptake of the intestine, causing glucose intolerance. A viral infection of the intestine also leads to a temporary IgA deficiency, causing larger amounts of food antigens to be present in the blood.

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