Mast cell mediators: Prostaglandin D2 (PGD2)

Prostaglandin D2 (PGD2) is the predominant prostaglandin product released by mast cells. It is found prevalently in the central nervous system and peripheral tissues, where it performs both inflammatory and normal processes. In the brain, PGD2 helps to regulate sleep and pain perception. PGD2 can be further broken down into other prostaglandins, including PGF2a; 9a, 11b-PGF2a (a different shape of PGF2a), and forms of PGJ. 9a, 11b-PGF2a shares the same biological functions as PGD2. Both of these can be tested for in 24 hour urine test as markers of mast cell disease.

PGD2 is a strong bronchoconstrictor. It is 10.2x more potent in this capacity than histamine and 3.5x more potent than PGF2a. It has been associated with inflammatory and atopic conditions for many years. Presence of allergen activates PGD2 production in sensitized people. In asthmatics, bronchial samples can achieve over 150x the level of PGD2 compared to controls. Elevated PGD2 has been associated with chronic coughing.

PGD2 is a driver of inflammation in many settings. It acts on bronchial epithelium to cause production of chemokines and cytokines. It also brings lymphocytes and eosinophils to the airway, which induces airway inflammation and hyperreactivity in asthmatics. PGD2 may also inhibit eosinophil cell death, resulting in further inflammation.

An interesting facet of PGD2 is its role in nerve pain. It has been found that PGD2 is produced by microglia in the spine after a peripheral nerve injury. These cells make more COX-1, which then makes PGD2. Newer COX-2 inhibiting NSAIDs do not affect nerve pain in mouse models, but older NSAIDs that inhibit COX-1 and COX-2 reduce neuropathy.

PGD2 is found to inhibit inflammation in other settings. It can reduce eosinophilia in allergic inflammation in mouse models. Additionally, once the acute phase of inflammation is over and it is resolving, administering a COX-2 inhibitor actually makes the inflammation worse. This indicates that PGD2 may be important in resolving inflammation in some processes.

Aspirin is commonly used in mast cell patients to inhibit prostaglandin production. PGD2 is primarily manufactured by COX-2, but the pathway that evokes neuropathy uses COX-1. There are a number of COX-1 and COX-2 inhibitors available.

In mast cell patients, PGD2 is probably most well known for causing flushing. This happens due to dilation of blood vessels in the skin. Due to a well characterized response to aspirin, this is generally the first line medication choice. Some salicylate sensitive mast cell patients undergo aspirin desensitization to be able to use this medication.

 

References:

Emanuela Ricciotti, Garret A. FitzGerald. Prostaglandins and Inflammation. Arterioscler Thromb Vasc Biol. 2011; 31: 986-1000.

Matsuoka T, Hirata M, Tanaka H, Takahashi Y, Murata T, Kabashima K, Sugimoto Y, Kobayashi T, Ushikubi F, Aze Y, Eguchi N, Urade Y, Yoshida N, Kimura K, Mizoguchi A, Honda Y, Nagai H, Narumiya S. Prostaglandin D2 as a mediator of allergic asthma. Science. 2000;287: 2013–2017.

G Bochenek, E Nizankowska, A Gielicz, M Swierczynska, A Szczeklik. Plasma 9a,11b-PGF2, a PGD2 metabolite, as a sensitive marker of mast cell activation by allergen in bronchial asthma. Thorax 2004; 59: 459–464.

Victor Dishy, MD, Fang Liu, PhD, David L. Ebel, BS, RPh, George J. Atiee, MD, Jane Royalty, MD, Sandra Reilley, MD, John F. Paolini, MD, PhD, John A. Wagner, MD, PhD, and Eseng Lai, MD, PhD. Effects of Aspirin When Added to the Prostaglandin D2 Receptor Antagonist Laropiprant on Niacin-Induced Flushing Symptoms. Journal of Clinical Pharmacology, 2009; 49: 416-422

11 Responses

  1. Kelly April 27, 2015 / 2:45 am

    oh my gosh!!! This article directly speaks to me. Bringing it w me to the docs in the am.
    You make my crazy world make sense.

  2. Jein.Noir September 26, 2015 / 6:26 pm

    As much as I like to look at studies myself; I’m probably enjoying your simplified explanations more. xD It’s nice to have all that information broken down in one place for when the brain-fog makes it impossible to read the complex stuff!

    In relation to your prostaglandins posts, I’m about to try Tylenol and/or other apirin options like white willow finally. I’ve just tried Singulair and found it to (amazingly not hurt, and help just a bit) not take out the major pain sources. Trying to narrow things down one chemical at a time since my Reishi has stopped working as well. I’m thinking it may help answer why certain herbs worked for me in the past. I may be returning to my former approach ~ lots of herbs. I dropped them all when my MCAD went out of control, but that may have been the wrong move….looking back, the triggers probably were the ferments and maybe the frequent consumption of nightshades. Unfortunately, when the itching started, I had no idea what I was trying to treat. Of course, without itching/rashes kicking in til years after the onset, my illness appeared to be due to a weak immune system with some horrific chronic infection (leading to antibiotic herbs and ferments galore.)

    Anyway, thanks for posting all this for everyone to have access to!

    ~Jane

  3. maria January 5, 2016 / 10:58 am

    Do you know where I might find the dosing guidelines for aspirin? I suspect I’m having issues with PGD2 and I’d like to do a trial with aspirin but I’m having trouble finding out how to properly dose it.

    Thanks in advance!

    • Lisa Klimas January 5, 2016 / 7:35 pm

      I’m not sure that there are truly guidelines, but I can look. I started at one 81mg aspirin daily, then twice a day after a few months. I now take 325mg in the morning and another 325mg as needed if symptoms are bad.

      • maria January 6, 2016 / 11:01 am

        Thank you so much for your reply Lisa! Do you think there’s any benefit to adjusting ones diets if prostaglandins are an issue. This post seems to suggest there is.

        http://www.endo-resolved.com/prostaglandins.html

        • Lisa Klimas January 6, 2016 / 2:32 pm

          Absolutely. Irritating mast cells less generally can mitigate symptoms from multiple mediators. Flushing is generally associated with PGD2 and is for many a reaction to eating many foods (myself included). When I avoid many foods, my flushing decreases.

          • Maria January 6, 2016 / 5:23 pm

            What kind of foods have you found helpful to avoid? I’m afraid to limit meat too much. I can live without dairy though

          • Lisa Klimas January 7, 2016 / 2:09 am

            Vinegar, alcohol, anything fermented. I wrote a long post about how I eat low histamine, it was published last June, I believe. A lot of foods that I react to don’t cause life threatening reactions. I don’t feel great after I eat them, but it’s not a massive reaction. Vinegar, alcohol and fermented items cause severe anaphylactic reactions. Also undercooked egg whites.

  4. Susan April 2, 2016 / 9:16 pm

    Undercooked egg whites? Ah, that explains a few past incidents.

  5. Alessandro Salvatori June 10, 2016 / 12:58 am

    Have you looked into palmitoylethanolamide and adelmidrol?

  6. Gloria June 29, 2016 / 8:28 am

    Hello,

    I have been dealing with severe itching on my back and sides and neck for over a year. It seemed to be connected to the beginning of menopause (stated last yr at 45), but now I’m not sure. My pgd2 came back low. Before that blood test, I’ve had about 35 tests, I diagnosed myself wth being allergic to histamine releasing foods. From this site, it seems people’s symptom is nerve pain… I’ve read others have coughing. Have you experienced itching/rash? I am pretty darn sure ascertain foods probably cause more itching but I swear sometimes it’s worse than others which I can’t figure out. Stress seems to be involved too but not entirely that is for sure.

    Thank you for your time!

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