Allergies and Naturopathic Treatment with a Focus on Modulating Cytokines

With the start of allergy season, many patients are interested in alternatives to the daily routine of popping an over-the-counter antihistamine.  Generally, patients have had to try a variety of types of these antihistamines to find one that works well for their symptoms.  Some have gone the route of using intra-nasal steroids as a way to control allergic rhinitis.  These patients end up in the office usually because of a disdain for the daily use of a synthetic drug, and are interested in natural alternatives.

There are definitely natural alternatives that have similar mechanisms of action as the over-the-counter drugs.  For example, quercetin has been widely used because of its known action in stabilization of the mast cell membrane, and subsequently lessens the release of histamine.1 This effect of quercetin can be enhanced by the use of a variety of herbal teas, including the commonly used herbs chamomile, saffron, anise, fennel, caraway, licorice, cardamom and black seed.2   Detoxification protocols may be implemented, as well as the use of oxidative therapies to encourage a more balanced immune response.

A general understanding of allergy, though a gross over-simplification, is that there is a cytokine imbalance in the immune system that general leads to a Th2-phenotypic dominance.3  This Th2 dominance is thus responsible for over-active B-cells and their subsequent production of an excess of immunoglobulin E.    It is the immunoglobulin E that triggers the allergic symptoms with the activation of cells such as the mast cells.  The Th1-Th2 balance theory is useful in clinical practice, but has its limitations, including that many cytokines do not fall neatly into one category versus the other.4

The first part of my approach to difficult allergic patients is to ascertain whether or not food sensitivities may be promoting the allergic phenotype.  I choose foods to evaluate first because of the control the patient has in choosing his or her exposure - for example it is much easier for the patient to avoid casein as opposed to staying away from environmental allergens such as grass.  The identification and elimination of food sensitivities may benefit environmental and seasonal allergies, although the mechanism is not completely understood.  One theory involves the limiting of Th2 cytokines.  For example, if the patient has an IgG or IgE protein directed against casein, every time the casein is ingested  in significant and frequent enough quantities it will elicit a release of cytokines such as IL-4 or IL-5.5  These cytokines can then increase Th2 cell activity in general, leading to the increased activity of more immunoglobulin including those that cause the seasonal allergic symptoms.6 

The second component of my treatment program involves detoxification of organic and heavy metal toxins.  While I recommend a combination of intense exercise to promote sweating, usually a compromise is made whereby alternating hot and cold showers (similar to constitutional hydrotherapy) is done.   Provoked testing for heavy metals is done using oral DMSA, oral DMPS, and IV CaEDTA.  The heavy metal lead has been shown to have a very distinct effect of polarizing towards an excessive Th2 response8,9 although this has been in mice.  

My third branch of treatment for allergic patients is the one that I have found most useful in the majority of patients.  This involves the use of the oxidative therapies.  Particularly, ultraviolet blood irradiation and ozone therapy by major autohemotherapy.  

Ozone therapy by major autohemotherapy is perhaps the most well-studied of these oxidative treatments when it comes to understanding the cytokines that are released during treatment.  In particular, Bocci has done a great review article10  in which he describes the biological effects, including cytokine release, that occur during this useful treatment.  In practice, major autohemotherapy is performed twice a week for 3 weeks and then the effect evaluated.  If positive, the treatment is tapered off to once a week to once every two weeks for 4 treatments, and then as needed or once every 1-2 months.  During the tapering period, aerobic exercise is prescribed in incrementally increasing durations and intensity.  The reason for this is that at intense aerobic exercise, as much as 5% of the oxygen consumed will not be completely reduced to water, and will contribute to direct oxidative stimulation of the cells.     


1. Kempuraj D, Madhappan B, Christodoulou S, Boucher W, Cao J, Papadopoulou N, Cetrulo CL, Theoharides TC. Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells.  Br J Pharmacol. 2005 Aug;145(7):934-44. 

2.Haggag EG, Abou-Moustafa MA, Boucher W, Theoharides TC. The effect of a herbal water-extract on histamine release from mast cells and on allergic asthma.  J Herb Pharmacother. 2003;3(4):41-54. 

3. Bisset LR, Schmid-Grendelmeier P. Chemokines and their receptors in the pathogenesis of allergic asthma: progress and perspective.  Curr Opin Pulm Med. 2005 Jan;11(1):35-42. Review. 

4. Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease.  Altern Med Rev. 2003 Aug;8(3):223-46. Review. 

5. de Jong EC, Spanhaak S, Martens BP, Kapsenberg ML, Penninks AH, Wierenga EA. Food allergen (peanut)-specific TH2 clones generated from the peripheral blood of a patient with peanut allergy.  J Allergy Clin Immunol. 1996 Jul;98(1):73-81. 

6. Gluck J, Rogala B, Mazur B.  Intracellular production of IL-2, IL-4 and IFN-gamma by peripheral blood CD3+ cells in intermittent allergic rhinitis.  Inflamm Res. 2005 Feb;54(2):91-5. 

7. Joneja JM. Food Allergy Testing: Problems in Identification of Allergenic Foods.  Can J Diet Pract Res. 1999 Winter;60(4):222-230. 

8. Iavicoli I, Carelli G, Stanek EJ 3rd, Castellino N, Calabrese EJ.  Below background levels of blood lead impact cytokine levels in male and female mice.  Toxicol Appl Pharmacol. 2006 Jan 1;210(1-2):94-9. Epub 2005 Nov 10. 

9. : Gao D, Kasten-Jolly J, Lawrence DA. Related Articles, Links 

The paradoxical effects of lead in interferon-gamma knockout BALB/c mice.  Toxicol Sci. 2006 Feb;89(2):444-53. Epub 2005 Nov 9.  

10. Bocci V. Ozone as Janus: this controversial gas can be either toxic or medically useful. Mediators of Inflammation, 2004 Feb;13(1), 3-11.