Immunologically Mediated Diseases and Allergic Reactions
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
Current therapies for allergy attempt to prevent the release of inflammatory mediators from mast cells or to interfere with the actions of such mediators. For example, antihistamines are administered to antagonize the binding of histamine to its receptors and to counteract the effects of histamine. Antihistamines inhibit the wheal and flare response, but they do not block constriction of smooth muscle. Sodium cromolyn benefits patients with allergic disorders, such as asthma, and is thought to inhibit inflammatory cell activation and mediator release. Epinephrine and theophylline also inhibit mast cell activation. In addition, these drugs counteract the effect of leukotrienes on smooth muscle by acting as bronchodilators. Prevention of bronchoconstriction is currently being attempted by administration of drugs that inhibit leukotriene synthesis and antagonize leukotriene receptors. Corticosteroids are the most potent anti-inflarnmatory drugs available. Corticosteroids not only diminish inflarnmatory cell activation and function, they also block the transcription of cytokine genes, including those for TNF and IL-4 production. Corticosteroids can be detrimental to health and produce undesirable effects, so they must be used with great care.
Irritable Bowel Syndrome
Nicole M. Farmer, Andres Victor Ardisson Korat in Cooking for Health and Disease Prevention, 2022
Cooking and food preparation methods can have an impact on some food constituents relevant in IBS. For example, as discussed above, food sensitivities (such as nonceliac gluten sensitivity) are thought to potentially be contributory to IBS (Ali et al. 2017). One proposed mechanism is thought to be low-level immunological reactions to triggering proteins (Cuomo et al. 2014). Studies suggest that baking can alter the immunologic properties of gluten and other cereal proteins (Smith et al. 2015). And, it isn’t just proteins affected, fiber quantity and form (soluble and insoluble) are impacted by cooking techniques as well. In one study, the steaming of vegetables caused a shift from insoluble to soluble fiber – in some cases by three-fold (Kalala et al. 2018). For IBS patients sensitive to food-derived histamine, selection of cooking methods may be important. Histamine formed in food is heat-stable and thus remains intact in cooked food. A study evaluating the effect of different cooking methods on histamine from namely seafood, processed meats, and fermented foods found that frying and grilling significantly increased measured histamine levels, whereas boiling, likely due to dilution, produced lower levels (Chun et al., 2017).
Anaphylaxis
Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial in Textbook of Allergy for the Clinician, 2021
Histamine is an important chemical mediator of allergic responses and the major clinical manifestations of anaphylaxis. Histamine is released by activated mast cells and basophils. Cutaneous histamine release causes urticaria and pruritus, while systemic release of histamine results in flushing, headache, bronchoconstriction, hypotension, tachycardia, as well as direct effects on coronary arteries and atrial and ventricular contractility (Reber et al. 2017). Histamine effects are mediated through four histamine receptors; H1, H2, H3 and H4, which are present on target cells in different organs (MacGlashan 2003). H1 and H2 receptors both mediate flushing, hypotension and headaches, whereas airway obstruction and tachycardia are primarily mediated via the H1 receptor (Kaliner et al. 1981, Vigorito et al. 1983). In animal models, H3 appears to influence cardiovascular response to norepinephrine, and H4 may be involved in chemotaxis, mast cell cytokine release and pruritus (Godot et al. 2007, Dunford et al. 2007).
The human NTG model of migraine in drug discovery and development
Published in Expert Opinion on Drug Discovery, 2023
Lanfranco Pellesi
Although events initiated by NTG are implicated in migraine, it is unclear which other mediators act together with NO. In 15 female migraine patients without aura, plasma CGRP was elevated during sublingual NTG-induced migraine [61]. CGRP levels correlated with migraine timing and severity and returned to baseline after the cessation of migraine. During NTG-induced migraine, plasma CGRP levels decreased parallel to headache intensity after intranasal administration of sumatriptan in 19 female migraine individuals [62]. In 10 healthy subjects, plasma CGRP evaluated from the jugular vein did not differ from baseline after a 20-minute NTG infusion (0.12 μg/kg/min) [63]. A small-molecule CGRP receptor antagonist (telcagepant) did not prevent sublingual NTG-induced vasodilation in 22 healthy males [64]. Another CGRP receptor antagonist (olcegepant) did not stop migraine provoked by a 20-minute NTG infusion (0.5 μg/kg/min) in 13 migraine individuals, suggesting that CGRP is not primarily involved in NTG-induced migraine [65]. Other mediators are apparently not involved in NTG-induced migraine, such as histamine and prostaglandin E2. Pre-treatment with a histamine 1 receptor blocker (mepyramine) did not prevent migraine episodes caused by a 20-minute NTG infusion (0.5 µg/kg/min) in seven migraine individuals [66]. Hence, prostaglandin E2 was not elevated after a 20-minute NTG infusion (0.5 µg/kg/min) in women with migraine, with plasma levels being similar among interictal, pre-ictal and ictal states [67].
Carbopol emulgel loaded with ebastine for urticaria: development, characterization, in vitro and in vivo evaluation
Published in Drug Delivery, 2022
Barkat Ali Khan, Arshad Ali, Khaled M. Hosny, Abdulrahman A. Halwani, Alshaimaa M. Almehmady, Muhammad Iqbal, Waleed S. Alharbi, Walaa A. Abualsunun, Rana B. Bakhaidar, Samar S. A. Murshid, Muhammad Khalid Khan
Histamine is one of the prominent mediators of most forms of urticaria; therefore, antihistamines (especially H1 antihistamines) are usually used for the treatment of patients with chronic urticaria (Harmalkar et al., 2019; Mehetre et al., 2019). Clinically, urticaria is found in all age groups. The wheals and flares develop within hours (or even sooner). The hives occur in episodes depending on the allergen and may last for a day or for weeks or months (Bhasha, 2013). Three kinds of triggers alter the allergic reaction or (urticaria) hives: (1) foods, including food additives, berries, nuts, eggs, sea foods, and dairy products, (2) medications (e.g. penicillin, sulfas, salicylate, vaccines, and anesthetics), and (3) environmental conditions (e.g. hot and cool weather, exercise, bee or wasp stings) (Paul et al., 1987).
Hypolipemic effects of histamine is due to inhibition of VLDL secretion from the liver: involvement of both H1 and H2-receptors
Published in Archives of Physiology and Biochemistry, 2022
Atefeh Nikfar, Mehdi Rasouli
Stimulation of lipolysis in adipose tissue is another way whereby histamine affects plasma lipids in vivo. In vivo experiments indicated that histamine stimulates lipolysis in fat tissue through H2-receptors and increases free fatty acids (Akiyama et al.1990). A similar result has been shown in the cultures of canine fat cells (Bugajski and Gadek 1985). A central histaminergic pathway also may be involved. It is well indicated that plasma free fatty acids stimulates directly the rate of VLDL secretion from the liver (Rasouli et al.2016). Lipolysis in adipocytes is mediated through the cAMP pathway, which is also used in the H2-histaminergic signal transduction pathway. Thus, histamine has two opposite effects on the plasma lipids in vivo. Stimulation of lipolysis is mediated by the cAMP pathway (i.e. H2-receptors) at fat tissue and subsequently increases VLDL secretion from the liver. While stimulation of either Ca2+/calmodulin (H1-receptors) or cAMP (i.e. H2-receptors) inhibits VLDL secretion directly in the liver (Rasouli et al.2016, Wang et al.2010). Imoto et al. also have reported that histamine H1 receptors are more predominant than H2-histamine, adrenergic, and prostaglandin receptors on the liver plasma membrane (Imoto et al.1985).