Attempting to understand the differences between histamine and leukotrienes in the treatment of allergic rhinitis

Spring has arrived. Which means for many allergy sufferers- allergic rhinitis or hay fever can make spring-filled days seem unbearable. Allergic rhinitis is an over-reaction of the immune system to particles in the air that a person breathes. This over-reaction causes inflammation. Incidentally, understanding the biology of hay fever has been at the forefront of the pharmaceutical industry for past five years. The primary difference between histamine and leukotriene and the treatment of allergic rhinitis, may be the identification and frequency of the symptoms that may take longer in comparison with the “immediate” symptoms. Hence, the jury is still in session on prescribing this type controlling agent for patients with allergic rhinitis. Medications like Singulair, Accolate and Zyflo (that have not been approved by the FDA for the treatment of allergic rhinitis) have appeared to increase in popularity with physicians when considering therapeutic modalities.

The most common “immediate” symptoms comprise sneezing, rhinorrhea (runny nose), post nasal drip and itchy eyes, ears and throat. Compared to symptoms that may take longer: congestion, altered sense of smell, chronic cough, issues with sinuses and the Eustachian tubes, and a sensitivity to light. The variation and frequency of symptoms occur only at certain times of the year and unfortunately, these symptoms remain for life.

Consequently, leukotrienes have received considerable attention during the past five years from pharmaceutical industry due to an increased understanding of the tenuous relationship between histamine and leukotrienes. Understanding the differences between histamine and leukotrienes would not only enhance research efforts in treating the variation of symptoms caused by allergic rhinitis; but also, allow researchers to understand the pathways that guide leukotrienes to function, as it relates to the biology of allergic rhinitis compared to asthma (first used to treat asthma).

Histamine is an important protein that is involved in many allergic reactions. Allergies are uniquely caused by an immune response to a normally innocuous substance such as pollen that comes in contact with lymphocytes specific for that substance (Janeway et al, 1999). Lymphocytes are small white blood cells that have the responsibility of carrying out the activities of the immune system; which validates their role with histamine production. What is unique about lymphocytes, particularly, B cells and how they work when the immune system is under attack. This process is known as humoral immunity. B cells work by secreting soluble fluids or humors. These antibodies typically interact with circulating antigens such as bacteria and other toxic molecules.

To better understand how we arrived at two classes of antileukotriene drugs (asthma and rhinitis) we must understand the pharmacogenetics of allergic disease. Leukotrienes belong to a group of hormones that cause the symptoms of allergic rhinitis. What is unique about leukotrienes, are the modifiers that prevent the production or action of leukotrienes, which are used to treat allergic rhinitis. Leukotrienes are often linked to asthma, due to being classified as one of the several substances that are released by mast cells during an asthma attack (Berger, 1999). As a result, drugs have been designed that can interfere with the activity of leukotriene receptors when an asthma attack occurs.

Leukotrienes use both autocrine signaling (cell secretes a hormone) and paracrine signaling (signaling affects cells of different types). In this light antileukotriene drugs also known as controller agents may also have the potential in treating patients that have symptoms that may take much longer. For example, patients that express complaints of chronic cough or sensitivity to light may benefit from taking this type of controller agent.

References

WebMD. [Online]. Allergies Health Center. Retrieved from http://www.webmd.com/allergies/tc/allergic-rhinitis-treatment-overview on March 25, 2008.

Janeway CA, Travers P, Walport M, Capra JD. Immunobiology: the Immune System in Health and Disease. 4th ed. London: Current Biology Publication; 1999. p 602.

Marone G, Granata F, Spadaro G, Onorati AM, Triggiani M. 1999. Antiinflammatory effects of oxatomide. Journal of Investigational Allergology and Clinical Immunology 9(4): 207-214.

Protein Data Bank. Structure Explorer – 1AVN. Accessed 2000 Mar 2.

Schmidt D, Ruehlmann E, Branscheid D, Magnussen H, Rabe KF. 1999 Aug. Passive sensitization of human airways increases responsiveness to leukotriene C4. European Respiratory Journal 14(2): 315-319.
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Berger, A. (1999). Science commentary: What are leukotrienes and how do they work in asthma? British Medical Journal 319 (7202) 90.


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