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Allergy and Inflammation

allergiesIf you’re among the susceptible, the first whack in the face by a giant pollen ball is enough to set you back.  You get the runny nose, the watery eyes, the headaches and all the accessories.  If they were temporary symptoms, you wouldn’t pay much attention.  A handful of tissues and a couple of antihistamines, and you’re on your way.  Few of us understand, though, that seasonal allergies incite an inflammatory response, which is a protective attempt by the body to remove the enemy and clean up the place where it was.  Inflammation is not infection, but may be caused by it.  It’s considered part of the innate immune system, which activates as a function of your natural biological makeup.

Allergic disorders, which include hay fever, eczema and asthma, afflict almost a quarter of the population in the developed world (Holgate, 1999) (Galli, 2008).  Persistent exposure to allergens, basically innocuous substances in the environment, results in chronic allergic inflammation.  This can cause the affected organ(s) to go through substantial changes in function.  In fact, some people can develop a potentially fatal systemic reaction, called anaphylaxis, within seconds of exposure to an allergen (Simons, 2011).  Certain foods, as well as other non-infectious substances, may be involved.  In allergic responses, allergen-specific immunoglobulin E (IgE) and T helper cells (Th2) are switched on.

An acute response to an allergen that happens after a single exposure is called an early-phase reaction, or a Type-1 immediate hypersensitivity reaction.  Histamine is released here during mast cell degranulation. These molecules hook up with IgE and eventually cause itching, mucus production, swelling of blood vessels (vasodilation), edema and the airway constriction seen in allergic asthma (Hansen, 2004)  (Katelaris, 2003).  Chronic inflammation may be characterized by a continuum of tissue destruction and healing that may lead to loss of function, but this is not often seen with seasonal allergies, called allergic rhinitis. Allergic rhinitis is linked to decreased learning, poor performance at work and school, and of course, reduced quality of life.  The course of action taken by a doctor offers several pharmacologic options (Sadeq, 2004), many of which are shunned by patients in favor of natural alternatives.  Allergen-specific immunotherapy is designed to suppress the mechanism that responds to allergen attack.  This entails the use of chemical agents to regulate body function (Fujita, 2012), and this engenders a jaundiced eye among the holistic crowd.

Within the domain of complementary and alternative medicine is a plant whose use predates medieval times—stinging nettle, scientifically known as Urtica dioica.   For hundreds of years it’s been used to treat gout, painful joints, arthritis, eczema and anemia.  In modern times, nettle has been used to treat urinary problems during the early stages of benign prostate hyperplasia, and to treat urinary infections and hay fever.  It’s also been used in compresses to address joint pains, sprains and strains, tendinitis and insect bites.  Freeze-dried preparations were matched against placebo in a double-blinded randomized allergic rhinitis study performed at the National College of Naturopathic Medicine, and were found to be more effective than placebo at relieving symptoms (Mittman, 1990).  Cytokines are regulatory proteins that are released by cells of the immune system, where they act as mediators in the generation of an immune response, and may be assayed by the measurement of Th1 and Th2 cells, as well as by other markers of immune activation.  Extracts of stinging nettle, registered in Germany for therapy of rheumatic disease, were found to inhibit the inflammatory cascade identified by these artifacts (Klingelhoefer, 1999).

Quercetin is a bioflavonoid derived from red wine, citrus, onions, parsley, apples and tea, demonstrating several noble qualities, anti-inflammation and anti-oxidation among them.  The anti-inflammatory property arises from its inhibition of the production and activity of leukotrienes and pro-inflammatory prostaglandins, and inhibition of histamine release by basophils and mast cells.  Additionally, quercitin represses expression of the COX2 enzyme that is responsible for the manufacture of pro-inflammatory substances, and it stems the interleukins that characterize inflammation (Nieman, 2007).  Studies at Northwestern University agree that quercitin has its place as a primary therapy or as an adjunct in the treatment of allergic rhinitis (Thornhill, 2000).  Ocular symptoms of allergy are uncomfortable and often more bothersome than nasal symptoms.  Japanese scientists found that quercitin, in a double-blind placebo-controlled study, was substantially more effective than placebo at ameliorating the ocular symptoms that can plague sufferers of allergic rhinitis.  Ocular scores that rated tearing, itching and ocular congestion were low, while nasal scores differed little from the control group (Hirano, 2009).

Complementary medicine is not without allies in the allopathic medical community, especially when a supplement has proven efficacy against a traditional modality.  In the conventional medical sector, where raised eyebrows are the norm after the mention of complementary approaches, bromelain, the proteolytic enzyme from pineapple that digests proteins and tenderizes meat, has found favor in the treatment of otolaryngology disorders that include allergic rhinitis.  In a multicenter trial composed of 116 children, bromelain monotherapy (used by itself) effected faster recovery from sinusitis compared with standard therapy (Karkos, 2007).  As adjunctive to traditional therapy, bromelain exhibited supportive strength against acute rhinosinusitis (Guo, 2006).  Although marketed as a digestive aid, bromelain appears to have systemic anti-inflammatory activity (Hale, 2005) (Kumakura, 1988) (Onken, 2008).

In recent announcements, oral vitamin D added to regular intranasal corticosteroid dosing improves symptoms beyond that seen with corticosteroids alone, leading researchers to conclude that vitamin D affords benefit to patients with allergies (Baroody, 2012).  Treating inflammation may be nearer at hand than previously thought, and that just might eliminate, or at least reduce, the misery of seasonal allergy.

References

Ahmadiafshar A, Taghiloo D, Esmailzadeh A, Falakaflaki B.
Nasal eosinophilia as a marker for allergic rhinitis: A controlled study of 50 patients.
Ear Nose Throat J. 2012 Mar;91(3):122-4.

F. M. Baroody, J. Lane, S. Watanabe, M. DeTineo, J. Pinto, R. M. Naclerio;
The Addition of Vitamin D (VitD) to an Intranasal Steroid (INS) Improves Control of Symptoms in Seasonal Allergic Rhinitis (SAR)
J ALLERGY CLIN IMMUNOL.  FEBRUARY 2012;  abstract 510

G. Walter Canonica, MD
Treating Asthma as an Inflammatory Disease
CHEST July 2006 vol. 130 no. 1 suppl 21S-28S

Fujita H, Meyer N, Akdis M, Akdis CA.
Mechanisms of immune tolerance to allergens.
Chem Immunol Allergy. 2012;96:30-8.

Fujita H, Soyka MB, Akdis M, Akdis CA.
Mechanisms of allergen-specific immunotherapy.
Clin Transl Allergy. 2012 Jan 5;2(1):2

Stephen J. Galli, Mindy Tsai & Adrian M. Piliponsky
The development of allergic inflammation
Nature 454, 445-454 (24 July 2008)

Granado-Serrano AB, Martín MA, Bravo L, Goya L, Ramos S.
Quercetin Attenuates TNF-Induced Inflammation in Hepatic Cells by Inhibiting the NF-κB Pathway.
Nutr Cancer. 2012 Mar 27.

Guo R, Canter PH, Ernst E.
Herbal medicines for the treatment of rhinosinusitis: a systematic review.
Otolaryngol Head Neck Surg. 2006 Oct;135(4):496-506.

Hale LP, Greer PK, Trinh CT, Gottfried MR.
Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease.
Clin Immunol. 2005 Aug;116(2):135-42.

Hansen I, Klimek L, Mösges R, Hörmann K.
Mediators of inflammation in the early and the late phase of allergic rhinitis.
Curr Opin Allergy Clin Immunol. 2004 Jun;4(3):159-63.

Hirano T, Kawai M, Arimitsu J, Ogawa M, Kuwahara Y, Hagihara K, Shima Y, Narazaki M, Ogata A, Koyanagi M, Kai T, Shimizu R, Moriwaki M, Suzuki Y, Ogino S, Kawase I, Tanaka T.
Preventative effect of a flavonoid, enzymatically modified isoquercitrin on ocular symptoms of Japanese cedar pollinosis.
Allergol Int. 2009 Sep;58(3):373-82. Epub 2009 May 25.

Holgate ST.
The epidemic of allergy and asthma.
Nature. 1999 Nov 25;402(6760 Suppl):B2-4.

Jaber R.
Respiratory and allergic diseases: from upper respiratory tract infections to asthma.
Prim Care. 2002 Jun;29(2):231-61.

Jutel M, Akdis CA.
T-cell regulatory mechanisms in specific immunotherapy.
Chem Immunol Allergy. 2008;94:158-77.

Karkos PD, Leong SC, Arya AK, Papouliakos SM, Apostolidou MT, Issing WJ.
‘Complementary ENT’: a systematic review of commonly used supplements.
J Laryngol Otol. 2007 Aug;121(8):779-82. Epub 2006 Nov 24.

Katelaris CH.
Ocular allergy: implications for the clinical immunologist.
Ann Allergy Asthma Immunol. 2003 Jun;90(6 Suppl 3):23-7.

Klingelhoefer S, Obertreis B, Quast S, Behnke B.
Antirheumatic effect of IDS 23, a stinging nettle leaf extract, on in vitro expression of T helper cytokines.
J Rheumatol. 1999 Dec;26(12):2517-22.

Kostyuk VA, Potapovich AI, Suhan TO, de Luca C, Korkina LG.
Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation.
Eur J Pharmacol. 2011 May 11;658(2-3):248-56.

Kumakura S, Yamashita M, Tsurufuji S.
Effect of bromelain on kaolin-induced inflammation in rats.
Eur J Pharmacol. 1988 Jun 10;150(3):295-301.

Mittman P.
Randomized, double-blind study of freeze-dried Urtica dioica in the treatment of allergic rhinitis.
Planta Med. 1990 Feb;56(1):44-7.

Nieman DC, Henson DA, Davis JM, Angela Murphy E, Jenkins DP, Gross SJ, Carmichael MD, Quindry JC, Dumke CL, Utter AC, McAnulty SR, McAnulty LS, Triplett NT, Mayer EP.
Quercetin’s influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA.
J Appl Physiol. 2007 Nov;103(5):1728-35. Epub 2007 Aug 23.

Obertreis B, Giller K, Teucher T, Behnke B, Schmitz H.
Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid.
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Jane E Onken, Paula K Greer, Brian Calingaert, Laura P Hale
Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro.
Clin Immunol. Volume 126, Issue 3, March 2008, Pages 345–352

Overman A, Chuang CC, McIntosh M.
Quercetin attenuates inflammation in human macrophages and adipocytes exposed to macrophage-conditioned media.
Int J Obes (Lond). 2011 Sep;35(9):1165-72.

Sadeq A. Quraishi, MHA;  Michael J. Davies, MD;  Timothy J. Craig, DO
Inflammatory Responses in Allergic Rhinitis: Traditional Approaches and Novel Treatment Strategies
J Am Osteopath Assoc May 1, 2004 vol. 104 no. 5 suppl 7S-15S

Simons FE.
Anaphylaxis pathogenesis and treatment.
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Skiepko R, Zietkowski Z, Tomasiak-Lozowska MM, Tomasiak M, Bodzenta-Lukaszyk A.
Bronchial hyperresponsiveness and airway inflammation in patients with seasonal allergic rhinitis.
J Investig Allergol Clin Immunol. 2011;21(7):532-9.

Thornhill SM, Kelly AM.
Natural treatment of perennial allergic rhinitis.
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tYoon JS, Lee HJ, Choi SH, Chang EJ, Lee SY, Lee EJ.
Quercetin inhibits IL-1β-induced inflammation, hyaluronan production and adipogenesis in orbital fibroblasts from Graves’ orbitopathy.
PLoS One. 2011;6(10):e26261.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Seasonal Allergies – Autumn In New York

seasonal-allergiesAutumn in New York might be a great song, but that’s about as far as it goes for allergy sufferers. In a city made from concrete and glass, you’d think it was easy to escape an attack by natural allergens, like pollen and mold. Ragweed is the chief culprit that arouses immune cells to churn out antibodies to its pollen. The subsequent biochemical reactions flood the bloodstream with histamine, the chemical that gives rise to the familiar allergy symptoms. One ragweed plant can produce a billion grains of pollen in a season, and the grains are so light that they can travel hundreds of miles on the gentlest waft of air. That is why a city made of concrete and glass is not immune to a covert pollen attack. To make matters worse, you can’t just move to the mountains. The ragweed will follow you.

What used to be an allergy season running from mid-August to September is now on the calendar from the first of August to the middle of October. Rising temperatures and elevated carbon dioxide levels extend the season. Trees, grasses and molds are not dismissed as causes of seasonal misery. Damp leaves harbor molds that are kicked up when hit by the rake. In school, kids are assaulted by dust mites that have waited all summer for company.

It’s generally accepted that allergies are triggered by a protein. When a cruising lymphocyte identifies a threat it launches a countermeasure against it. In this complicated biochemical process antibodies are made. The particular antibody for allergic reactions is called immunoglobin E, or IgE, which attaches itself to mast cells and basophils, the cells that activate and release histamine. Histamine opens the flood gates of response, and blood vessels dilate, causing blood pressure to drop. The spaces surrounding cells fill with fluid and the symptoms begin—itching, hives, sneezing, wheezing, and more. In severe cases, anaphylactic shock may occur, a reaction that can be fatal if not handled immediately. The Epi-Pen addresses anaphylaxis. It contains epinephrine, a natural hormone that counteracts dangerous physiological changes that appear during allergic response.

Conventional treatments for allergies include steroid nasal sprays, antihistamines, decongestants, eye drops and shots. They’re used before, during and after symptoms occur. Rhinitis, characterized by irritated mucous membranes of the nose, is a common sign of seasonal allergy that responds to alternative measures, notably to butterbur. Butterbur rhizome extracts that are free of pyrrolizidine alkaloid hepatotoxic constituents have been found safe to use for up to four months (Schapowal, 2005), though many people use them longer. Pyrrolizidine alkaloids are produced by plants to protect them against insect herbivores, but are a danger to the liver, occluding small blood vessels and causing the organ to swell. Petasin, the active ingredient in butterbur, is an anti-inflammatory compound with relaxant properties (Ko, 2001), able also to inhibit histamine and leukotrienes, the latter being white blood cell components responsible for allergic and inflammatory reactions (Thomet, 2002).

Cetirizine is Zyrtec, the antihistamine that addresses the symptoms of allergic rhinitis. A quickened heartbeat, weakness or tremors, problems with urination, insomnia and dizziness are among its side effects. Butterbur, on the other hand, is generally well tolerated, although belching may occur, and those who are sensitive to some plant compounds may experience itching and mild rash. The fatigue and drowsiness common to cetirizine are absent. In a randomized study conducted in Switzerland, seasonal rhinitis patients receiving butterbur fared as well as those receiving cetirizine, without any of the sedative effects (Schapowal, 2002).

Nasal irrigation is the practice of using a fluid-filled vessel to flush excess mucus and debris from the nose and sinuses. Advocates insist that it promotes nasal and sinus health. The saline solution that is commonly employed may act as an antibacterial agent, as well. Being inexpensive and simple, the practice has gained considerable acceptance among Canadian and American medical practitioners, who agree that it could reduce reliance on antibiotics (Papsin, 2003) and antihistamines (Garavello, 2003). If it relieves symptoms, it’s a welcome ritual.

There is a plant chemical that acts simultaneously as a bronchodilator and an inhibitor of histamine and other allergic or pro-inflammatory chemicals in the body—quercetin, a compound common to apples, onions, dill, Hungarian peppers, capers and radishes. How’s that for diversity? Quercetin is a flavonoid, one of several substances known years ago as vitamin P, a designation that has fallen from favor. Flavonoids are noted for the coloration of many flowers designed to attract pollinators. In the higher plants, they act as chemical messengers, cell cycle inhibitors and directors of the total physiological machinery. Good for us is that these properties translate to humans, although they are slow to be recognized by the FDA and its European counterparts, primarily because absorption is an issue and clinical studies are few.

Where funding was available, outside the realm of pharmaceutical giants, quercetin and its comrades were found to demonstrate several pharmacological effects, including anti-viral, anti-microbial, anti-inflammatory and anti-allergic potential. These properties demonstrate a capability to down-regulate and to suppress certain of the many inflammatory pathways, including those involved in allergic inflammation and basophil enlistment (Chirumbolo, 2010). Of the flavonoids, quercetin is the most abundant, but has received the most attention because its effects on basophils are seen at billionth of mole concentrations, where studies in Italy learned that quercetin was able to sequester histamine release in activated cells (Chirumbolo, Marzotto, et al, 2010). Using mast cells sensitized with IgE, Japanese scientists learned that flavonoid varieties akin to quercetin display similar activity by inhibition of the calcium influx that signals the release of histamine and pro-inflammatory mediators (Kimata, 2000) (Kawai, 2007).

A regimen consisting of herbal interventions and dietary flavonoids (there are many to pick from) presents a complementary / alternative approach to the management of allergic misery with considerable effectiveness. Maybe it’s worth a try and you’ll save money on tissues.

References

Balabolkin II, Gordeeva GF, Fuseva ED, Dzhunelov AB, Kalugina OL, Khamidova MM.
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Chirumbolo S.
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Chirumbolo S, Marzotto M, Conforti A, Vella A, Ortolani R, Bellavite P.
Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets.
Clin Mol Allergy. 2010 Sep 17;8:13.

Garavello W, Romagnoli M, Sordo L, Gaini RM, Di Berardino C, Angrisano A.
Hypersaline nasal irrigation in children with symptomatic seasonal allergic rhinitis: a randomized study.
Pediatr Allergy Immunol. 2003 Apr;14(2):140-3.

Hirano T, Kawai M, Arimitsu J, Ogawa M, Kuwahara Y, Hagihara K, Shima Y, Narazaki M, et al
Preventative effect of a flavonoid, enzymatically modified isoquercitrin on ocular symptoms of Japanese cedar pollinosis.
Allergol Int. 2009 Sep;58(3):373-82.

Kawai M, Hirano T, Higa S, Arimitsu J, Maruta M, Kuwahara Y, Ohkawara T, Hagihara K, Yamadori T, Shima Y, Ogata A, Kawase I, Tanaka T.
Flavonoids and related compounds as anti-allergic substances.
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Kimata M, Shichijo M, Miura T, Serizawa I, Inagaki N, Nagai H.
Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells.
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Ko WC, Lei CB, Lin YL, Chen CF.
Mechanisms of relaxant action of S-petasin and S-isopetasin, sesquiterpenes of Petasites formosanus, in isolated guinea pig trachea.
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Mainardi T, Kapoor S, Bielory L.
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Middleton E Jr, Drzewiecki G.
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Papsin B, McTavish A.
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Schapowal A; Petasites Study Group.
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Schapowal A; Study Group.
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Thomet OA, Schapowal A, Heinisch IV, Wiesmann UN, Simon HU.
Anti-inflammatory activity of an extract of Petasites hybridus in allergic rhinitis.
Int Immunopharmacol. 2002 Jun;2(7):997-1006.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.