What do histamines cause

These investigators also showed that H3R can be involved in blood—brain barrier function. The H3R has also been associated with rhinitis This is likely because it is expressed on presynaptic nerves in the peripheral sympathetic adrenergic system and also on nasal sub-mucosal glands.

Stimulation of H3R suppressed norepinephrine release at presynaptic nerve endings and stimulated nasal sub-mucosal gland secretion Currently, several H3R ligands are available, but not in clinical use. H3R antagonists, such as clobenpropit and thioperamide, were extensively used as a research tools and few early stage clinical trial reports are also available for H3R antagonists However, these antagonists are used to treat obesity, myocardial ischemic arrhythmias, cognition disorders, and insomnia H4R mediates the pro-inflammatory responses of histamine in both autocrine and paracrine manners.

Histamine enhances adhesion molecule expression, cell shape change, and cytoskeletal rearrangement via H4R, leading to the increased migration of eosinophils 5. Histamine H4R stimulation of mast cells may have three positive effects. First, it increases chemotaxis of mast cells thus encouraging their accumulation at the site of an allergic response 6.

Third, it mobilizes intracellular calcium to either prime mast cells for activation or, indeed, induce degranulation. These effects have been studied using histamine, the H4R-agonist 4-methylhistamine, the H4R-antagonists thioperamide or JNJ and mast cells from H4R-deficient mice. Basophils also express H4R on their surface and release histamine following antigen stimulation However, basophils and mast cells differ in several important aspects, such as anatomical localization, the production of cytokines, and antigen-presenting activity.

Histamine, acting via H4R, induces chemotaxis of bone marrow-derived basophils. H4R may play significant roles in basophil regulation in allergic dermatitis H4R may be involved in the pathogenesis of allergy and inflammation by activating Th2 as well as Th17 cells 68 , Stimulation of H4R can also enhance the migration of eosinophils and the recruitment of mast cells leading to the amplification of immune responses and chronic inflammation. Similarly, H4R are involved in T cell differentiation and dendritic cell activation and its immunomodulatory function 6.

Histamine and selective H4R agonists were shown to induce the shape change of eosinophils, an effect that maybe blocked by selective H4R antagonists 5. Treatment with JNJ H4R antagonist resulted in a statistically significant inhibition of eosinophil shape change.

These results showed that administration of H4R antagonists may have an impact on eosinophil function Finally, the activation of H4R involves several signaling cascades for the release of various allergic inflammatory mediators.

ERK is a member of MAPK family and mediates the proliferation, differentiation, anti-apoptosis, regulation, and cytokine expression at gene level. In addition to H1R, H4R is considered as a novel drug target for the treatment of allergy and inflammation. Recently, the H4R antagonists such as JNJ and JNJ have been extensively used as a tools to understand the pathophysiological involvement of H4R and have been studied extensively in both cell culture and in vivo animal models , Furthermore, H4R antagonists have been used to explore the role of H4R in allergic inflammatory disorders, such as allergic asthma, allergic rhinitis, and chronic pruritus Mast cells play an active role in various allergic diseases such as acute pruritus, atopic dermatitis, allergic asthma, allergic rhinitis, and pulmonary fibrosis , H 1 -antihistamines, such as azatadine, cetirizine, and mizolastine are used for the treatment mast cell activated diseases Cimetidine, ranitidine, famotidine, and nizatidine are H2R selective antihistamines that reduce gastric acid secretion H3R antihistamines include thioperamide, clobenpropit, BF2.

JNJ is a selective H4R antihistamine that is widely used in inflammation and pruritus H 1 -antihistamines are a standard treatment for mast cell-mediated allergic diseases.

There is increasing evidence that histamine binding to H4 receptors exacerbates allergy and inflammation. Indeed, mast cells themselves have H4 receptors which when stimulated increased degranulation and cytokine production.

Therefore, antihistamines targeting both the H1 and H4 receptor could be an effective treatment for mast cell-mediated allergic diseases Pharmacological properties of H4R have been exhibited by various H4R transfected cells 87 , 89 , 99 , , However, some H3R ligands such as imetit, clobenpropit, thioperamide, and R -methylhistamine are also able to bind to the H4R with different affinities.

Currently, a number of H4R antagonists have been developed but only a few are undergoing clinical trials. JNJ , a potent and selective H4R antagonist, has shown impressive results in different allergic inflammatory diseases such as dermatitis, asthma, pruritus, and arthritis , Interestingly, the combination therapy of this H4R antagonist and the H1R antihistamine, cetirizine, showed a more beneficial effect in the treatment of pruritus as compared with H1R alone — Furthermore, a study was carried out by using JNJ to treat persistent asthma NCT , but no results have yet been reported.

However, a study in rheumatoid arthritis NCT was terminated due to issues related to efficacy. The recent developments in research on histamine pathway underscore the importance of histamine in allergic inflammation through its effects on the H1R and H4R. Although, drugs targeting H1R are being explored for the treatment of various mast cell-associated allergic disorders, they are not always clinically effective. Several H4R antagonists have entered the later stages of clinical trials for a different range of allergic and inflammatory diseases.

However, their clinical efficacy reports are not yet published. Furthermore, there appears to be some overlap in function between H1R and H4R, opening up the possibility for using synergistic strategies for therapeutic approaches.

As such, we suggest the combination therapies by using both H4R together with H1R antagonists may provide a potential benefit in the treatment of various allergic and inflammatory diseases. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Rothenberg ME. N Engl J Med — Kay AB. Allergy and allergic diseases.

First of two parts. N Engl J Med —7. Nature —6. Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor. Histamine induces cytoskeletal changes in human eosinophils via the H 4 receptor. Br J Pharmacol — Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. J Pharmacol Exp Ther — Identification of a histamine H4 receptor on human eosinophils — role in eosinophil chemotaxis.

J Recept Signal Transduct Res — A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties.

Inflamm Res — Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature —5. Histamine upregulates Th1 and downregulates Th2 responses due to different patterns of surface histamine 1 and 2 receptor expression. Int Arch Allergy Immunol —2. Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H1 receptors.

J Immunol — Enhancement of neutrophil infiltration in histidine decarboxylase-deficient mice. Immunology — Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Functional expression of H4 histamine receptor in human natural killer cells, monocytes, and dendritic cells. Histamine and its receptors. Br J Pharmacol Suppl 1 :S— Apoptosis in the airways: another balancing act in the epithelial program.

Histamine in allergic inflammation and immune modulation. Int Arch Allergy Immunol — Histamine receptors are hot in immunopharmacology. Eur J Pharmacol — Int Immunopharmacol — Mast cell functions in the innate skin immune system.

Immunobiology — Saito H. Mast cell research. Chem Immunol Allergy — Mast cells. Physiol Rev — Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors.

Biochem Biophys Res Commun —8. Theoharides TC. The mast cell: a neuroimmunoendocrine master player. Int J Tissue React — PubMed Abstract Google Scholar. Critical role of mast cells in inflammatory diseases and the effect of acute stress. J Neuroimmunol — Tal M, Liberman R. Local injection of nerve growth factor NGF triggers degranulation of mast cells in rat paw.

Neurosci Lett — Mol Immunol —5. Barnes PJ. Histamine receptors in the lung. Agents Actions Suppl — In food allergies it can cause vomiting and diarrhea.

And it constricts muscles in the lungs, making it harder to breathe. Most worrisome is when histamine causes anaphylaxis, a severe reaction that is potentially fatal. Swollen airways can prevent breathing, and a rapid drop in blood pressure could starve organs of vital blood. Antihistamines block cells from seeing histamine and can treat common allergies. Medicines like steroids can calm the inflammatory effects of allergies. And anaphylaxis needs to be treated with a shot of epinephrine, which opens up airways, and increases blood pressure.

Great progress is being made in understanding allergy triggers and managing allergic symptoms, and figuring out why histamine, our frenemy, acts the way it does. Find out specific up-to-date research and stories from medlineplus.

View this video on the MedlinePlus playlist at the U. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health. Histamine: The Stuff Allergies are Made of. Play Video. Some examples of these drugs include:.

Meanwhile, over-the-counter and prescription nonsteroidal anti-inflammatory drugs can affect how the body metabolizes histamine. In addition, high alcohol consumption and health conditions that damage the lining of the gut can lead to histamine intolerance.

A medical professional may have trouble defining and diagnosing histamine intolerance. This may be because the symptoms can arise in many different areas of the body and overlap with those of other conditions.

The symptoms can affect the lungs, skin, and brain, for example, but gastrointestinal symptoms, such as bloating, are most common. Almost all foods and drinks contain some histamine. The amount usually increases as the food ages, spoils, or ferments. Some foods and drinks also contain compounds that help release histamine in the body or block the production or effectiveness of the enzymes DAO and HNMT.

Many kinds of bacteria, including common food contaminants, can also produce histamine in the gut. In addition to producing histamine, certain bacteria can affect the health of the intestinal walls.

This may lead to intestinal barrier dysfunction in people with histamine intolerance. If they suspect an intolerance, a doctor may recommend a low histamine diet. Usually, this means limiting the intake of histamine-rich foods rather than excluding them entirely. Studies have found that trying this diet can be important in confirming a diagnosis of the intolerance. It may also improve the symptoms. Anyone with a low-histamine diet should focus on variety to make sure that they have adequate nutrition.

Several vitamins and minerals are necessary for DAO to function properly. Some can even increase DAO activity.

For this reason, people with histamine intolerance may benefit from consuming more foods and drinks rich in these nutrients. A person may also benefit from taking these supplements.