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The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, part 8

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

14. Are there any special instructions for the tests to diagnose mast cell disease?
• There are a lot of tests used to diagnose mast cell disease. There are certainly people who slip through the cracks with the current diagnostic criteria.
• The biopsy forms the centerpiece of diagnosis of both cutaneous and systemic forms of mastocytosis.
You can increase your chance of positive skin biopsy by choosing either a permanent lesion or an area of skin that is frequently reactive.
• For internal organs, including bone marrow, you can’t always tell where to biopsy just by looking. The area may look normal but show inflammation when viewed with a microscope.
• If patients do not need to take daily corticosteroids because they do not make their own (adrenal insufficiency or Addison’s disease), they are often recommended to not use corticosteroids (prednisone or similar) for five days before a bone marrow biopsy. Taking corticosteroids can tell your body to make a lot of extra white blood cells which can make it harder to give a correct diagnosis.
• The CKIT D816V mutation test is often done on a blood sample. It is much more accurate when a bone marrow biopsy is tested because there are many more mast cells. Mast cells do not live in the blood so the blood test is less accurate. If the test is positive in blood, we assume that the patient is truly positive. If the test is negative in blood, we are not sure if the patient is truly negative.
• Serum tryptase is a test with a lot of caveats. It is influenced heavily by timing and patient factors like weight. Many people with mast cell disease have normal serum tryptase. It is good for tracking progression of disease in patients with systemic mastocytosis.
• About 85% of patients with systemic mastocytosis have a baseline tryptase value over 20 ng/mL. Patients with monoclonal mast cell activation syndrome may also have baseline tryptase value over 20 ng/mL. For these patients, they should have two different tests from days when they are not especially reactive, or have had anaphylaxis.
• For patients with mast cell activation syndrome, we are often looking for an increase in tryptase during a reaction or anaphylactic event. In these patients, experts recommend having blood drawn 15 minutes to 4 hours after onset of the event.
• Another sample should be drawn 1-2 days later so that you have a sample to compare with the tryptase level during the event. Many experts accept a level increased by 20% plus 2 ng/mL above the baseline to be indicative of mast cell activation. (I made a typo on this that said 20% to 2 – sorry!)
• As we have previously discussed, many mast cell mediators should be kept cold because they break down quickly. 24 hour urines for n-methylhistamine, prostaglandin D2, 9a,11b prostaglandin F2, and leukotriene E4 should be kept cold.
Performing a 24 hour urine when you are having a reaction event can increase the likelihood of mediator release.
COX inhibitors will interfere with prostaglandin production. Some patients stop these meds before giving 24 hour urines for prostaglandin testing. DO NOT STOP MEDS WITHOUT BEING ADVISED BY AN EXPERIENCED MAST CELL PROVIDER.
Lipoxygenase inhibitors will interfere with leukotriene production. Some patients stop these meds before giving 24 hour urines for leukotriene testing. DO NOT STOP MEDS WITHOUT BEING ADVISED BY AN EXPERIENCED MAST CELL PROVIDER.
• Heparin is very heat sensitive. Plasma heparin must be kept cold. One study reported that a tourniquet on the upper arm for ten minutes before drawing the sample increased the change of detecting mast cell activation with this test.
• Chromogranin A is influenced by many other conditions and medications. It is important that those other conditions be ruled out. This may require lengthy body scans and other tests. Chromogranin A is influenced by proton pump inhibitors, meds that are commonly taken by mast cell patients. DO NOT STOP MEDS WITHOUT BEING ADVISED BY AN EXPERIENCED MAST CELL PROVIDER.

For more detailed reading, please visit these posts:

The Provider Primer Series: Mediator testing

Patient questions: Everything you wanted to know about tryptase

The Provider Primer Series: Mast cell activation syndrome (MCAS)

The Provider Primer Series: Cutaneous Mastocytosis/ Mastocytosis in the Skin

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (SM-AHD, MCL, MCS)

The Provider Primer Series: Mediator testing

Evidence of mediator release

  • Mast cells produce a multitude of mediators including tryptase, histamine, prostaglandin D2, leukotrienes C4, D4 and E4, heparin and chromogranin A[i].
  • Objective evidence of mast cell mediator release is required for diagnosis of MCAS (Castells 2013)[ii], (Akin 2010)[iii], (Valent 2012)[iv].
  • Serum tryptase and 24 hour urine testing for n-methylhistamine, prostaglandin D2, prostaglandin 9a,11b-F2 are frequently included in MCAS testing recommendations (Castells 2013)[ii], (Akin 2010)[iii], (Valent 2012)[iv].
  • It can be helpful to test for other mast cell mediators including 24 hour urine testing for leukotriene E4[v]; plasma heparin[ix]; serum chromogranin A[ix]; and leukotriene E4[ix].


  • Tryptase is extremely specific for mast cell activation in the absence of hematologic malignancy or advanced kidney disease. Of note, rheumatoid factor can cause false elevation of tryptase[ix].
  • Serum tryptase levels peak 15-120 minutes after release with an estimated half-life of two hours[vi].
  • Per key opinion leaders, tryptase levels should be drawn 15 minutes to 4 hours after onset of anaphylaxis or activation event (Castells 2013[ii]), (Akin 2010[iii]), (Valent 2012)[iv]). Phadia, the manufacturer of the ImmunoCap® test to quantify tryptase, recommends that blood be drawn 15 minutes to 3 hours after event onset[vii].
  • Serum tryptase >11.4 ng/mL is elevated[i]. In addition to measuring tryptase level during the event, another sample should be drawn 24-48 hours after the event, and a third sample drawn two weeks later. This allows comparison of event tryptase level to baseline[vi].
  • An increase in serum tryptase level during an event by 20% + 2 ng/mL above patient baseline is often accepted as evidence of mast cell activation[v],[i].
  • Absent elevation of tryptase level from baseline during an event does not exclude mast cell activation[viii].
  • Sensitivity for serum tryptase assay in MCAS patients was assessed as 10% in a 2014 paper[ix].
  • A recent retrospective study of almost 200 patients found serum was elevated in 8.8% of MCAS patients[x].
  • Baseline tryptase >20.0 ng/mL is a minor criterion for diagnosis of systemic mastocytosis. 77-85% of SM patients have baseline tryptase >20.0 ng/mL[ix].

Histamine and degradation product n-methylhistamine

  • N-methylhistamine is the breakdown product of histamine.
  • Histamine is degraded quickly. Samples should be drawn within 15 minutes of episode onset[vii].
  • Serum histamine levels peak 5 minutes after release and return to baseline in 15-30 minutes[vii].
  • Sample (urine or serum) must be kept chilled[xi].
  • In addition to mast cells, histamine is also released by basophils. Consumption of foods or liquids that contain histamine can also inflate the level when tested[ix].
  • A recent retrospective study of almost 200 patients found that n-methylhistamine was elevated in 7.4% of MCAS patients in random spot urine and 5.4% in 24-hour urine[xi].
  • Sensitivity of 24-hour n-methylhistamine for MCAS was assessed as 22% in 24-hour urine[ix].
  • Plasma histamine was elevated in 29.3% of MCAS patients[xi].
  • 50-81% of systemic mastocytosis patients demonstrate elevated n-methylhistamine in 24-hour urine[ix].

Prostaglandin D2 and degradation product prostaglandin 9a,11b-F2

  • 9a,11b-prostaglandin F2 is the breakdown product of prostaglandin D2.
  • Prostaglandin D2 is only produced in large quantities by mast cells. Basophils, eosinophils and other cells produce minute amounts[ix].
  • A recent retrospective study of almost 200 patients found that PGD2 was elevated in 9.8% of MCAS patients in random spot urines and 38.3% in 24-hour urine[xi].
  • PGD2 was elevated in 13.2% of MCAS patients in plasma[xi].
  • 9a,11b-PGF2 was elevated in 36.8% in 24-hour urine[xi].
  • 62-100% of systemic mastocytosis patients demonstrate elevated prostaglandin D2 or 9a,11b-PGF2 in urine[ix].
  • Prostaglandins are thermolabile and begin to break down in a minutes. This can contribute to false negative results[xi].
  • Medications that inhibit COX-1 and COX-2, such as NSAIDs, decrease prostaglandin production[xi].

Leukotriene E4

  • Leukotriene E4 is produced by mast cells and several other cell types[ix] including eosinophils, basophils and macrophages.
  • A recent retrospective study of almost 200 patients found that LTE4 was elevated in 4.4 % of MCAS patients in random spot urines and 8.3% in 24-hour urine[xi].
  • 44-50% of systemic mastocytosis patients demonstrate elevated leukotriene E4 in urine[ix].
  • Medications that inhibit 5-LO, such as lipoxygenase inhibitors, decrease leukotriene production[xii].

Chromogranin A

  • Chromogranin A is produced by mast cells and several other cell types including chromaffin cells and beta cells.
  • Proton pump inhibitors can cause increased values during testing[xi].
  • A 2014 paper reported chromogranin A was elevated in 12% of MCAS patients and 63% of systemic mastocytosis patients tested[ix].


  • Heparin is a very specific mediator for mast cell activation[ix].
  • Heparin is extremely heat sensitive. The sample must be kept on ice or refrigerated at all times[ix].
  • Venous occlusion of upper arm for ten minutes has been successful in provoking mast cell activation leading to heparin release[ix].
  • A 2014 paper reported plasma heparin was elevated in 59% of MCAS patients and 47% of systemic mastocytosis patients tested[ix].
  • A recent retrospective study of almost 200 patients found that plasma heparin was elevated in 28.9% tested[ix].



[i] Theoharides TC, et al. (2012). Mast cells and inflammation. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, 1822(1), 21-33.

[ii] Picard M, et al. (2013). Expanding spectrum of mast cell activation disorders: monoclonal and idiopathic mast cell activation syndromes. Clinical Therapeutics, 35(5), 548-562.

[iii] Akin C, et al. (2010). Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol, 126(6), 1099-1104.e4

[iv] Valent P, et al. (2012). Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol, 157(3), 215-225.

[v] Lueke AJ, et al. (2016). Analytical and clinical validation of an LC-MS/MS method for urine leukotriene E4: a marker of systemic mastocytosis. Clin Biochem, 49(13-14), 979-982.

[vi] Payne V, Kam PCA. (2004). Mast cell tryptase: a review of its physiology and clinical significance. Anaesthesia, 59(7), 695-703.

[vii] Phadia AB. ImmunoCAP® Tryptase in anaphylaxis. Retrieved from:

[viii] Sprung J, et al. (2015). Presence or absence of elevated acute total serum tryptase by itself is not a definitive marker for an allergic reaction. Anesthesiology, 122(3), 713-717.

[ix] Vysniauskaite M, et al. (2015). Determination of plasma heparin level improves identification of systemic mast cell activation disease. PLoS One, 10(4), e0124912

[x] Zenker N, Afrin LB. (2015). Utilities of various mast cell mediators in diagnosing mast cell activation syndrome. Blood, 126(5174).

[xi] Afrin LB. “Presentation, diagnosis and management of mast cell activation syndrome.”  Mast Cells, edited by David B. Murray, Nova Science Publishers, Inc., 2013, 155-231.

[xii] Hui KP, et al. (1991). Effect of a 5-lipoxygenase inhibitor on leukotriene generation and airway responses after allergen challenge in asthmatic patients. Thorax, 46, 184-189.

The effects of cortisol on mast cells: Part 2 of 3

Glucocorticoids, like cortisol, can affect mast cells in many ways. As I discussed in my previous post, there are many ways for mast cells to release mediators when activated. In all of these pathways, there are many molecules involved that carry the signal, like people passing the Olympic torch. In mast cells, one of the molecules that suppresses inflammatory activation signal is called SLAP (yes, really).  Cortisol increases the amount of SLAP in mast cells so inflammatory activation signals are suppressed.

An important step in degranulation is changing the amount of calcium inside the cell and moving it to different parts of the cell. In some studies, glucocorticoids can affect this movement of calcium. Other studies have found that in some pathways, glucocorticoids don’t affect calcium movement, but instead interfere with things like the IgE receptor.

Cortisol is also thought to directly inhibit stem cell factor (SCF) binding to the CKIT receptor. When SCF binds to the CKIT receptor, this sends a signal to the mast cell to stay live.  This means that taking glucocorticoids can let mast cells die at the appropriate time. SCF also tells mast cells to go to inflamed spaces.  By blocking this signal, glucocorticoids suppress inflammation.

One of the ways that molecules carry a signal is by changing the next molecule in the pathway. A big way that cells changing molecules is by chopping off a piece of them called a phosphate group.  This is done by special enzymes called phosphatases.  Glucocorticoids affect the availability of phosphatases so they aren’t able to get to the right part of the cell to carry the signal.  When this happens, there is less activation and less histamine release.

Arachidonic acid is the molecule modified to make eicosanoids (leukotrienes, thromboxanes and prostaglandins.) Glucocorticoids directly interfere with the production of these molecules in multiple ways.  The first way is by interfering with COX-2, one of the enzymes that makes prostaglandins.  Another way is by preventing arachidonic acid from being released to a place where they can be turned into leukotrienes, thromboxanes and prostaglandins.  This occurs because glucocorticoids increase the amount of a powerful anti-inflammatory molecule called annexin-I.  Annexin-I inhibits the molecule that releases the arachidonic acid, called phospholipase A2.

Annexin-I was the subject of an important paper earlier this year. In trying to identify exactly how mast cell stabilizers like ketotifen and cromolyn work, the researchers discovered that treatment with mast cell stabilizers decreased degranulation and increased annexin-I made by mast cells.  They also found that glucocorticoids had the same effect.


Oppong E, et al. Molecular mechanisms of glucocorticoid action in mast cells. Molecular and Cellular Endocrinology 2013: 380, 119-126.

Varghese R, et al. Association among stress, hypocortisolism, systemic inflammation and disease severity in chronic urticaria. Ann Allergy Asthma Immunol 2016: 116, 344-348.

Zappia CD, et al. Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways. Scientific Reports 2015: 5.

Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011: 335(1), 2-13.

Sinniah A, et al. The role of the Annexin-A1/FPR2 system in the regulation of mast cell degranulation provoked by compound 48/80 and in the inhibitory action of nedocromil. International Immunopharmacology 2016: 32, 87-95.

Cardiovascular manifestations of mast cell disease: Part 3 of 5

Recurrent or perpetual elevation in blood pressure has been observed in multiple studies and may affect up to 31% of patients with mast cell activation disease (systemic mastocytosis, mast cell activation syndrome/disorder, monoclonal mast cell activation syndrome). Despite this high prevalence, many providers continue to believe that this symptom cannot be inherently from mast cell activation.

A number of mast cell mediators are vasoconstrictors, narrowing the blood vessels and elevating blood pressure. Histamine can both increase and lower blood pressure depending on which receptor it acts upon (H1: hypotension; H2: hypertension).

Several mediators participate in the angiotensin-renin pathway. Angiotensin II, the level of which is largely determined by mast cell mediators like renin, strongly elevates blood pressure. Chymase, involved in the angiotensin-renin pathway, can also either increase or lower blood pressure depending on concentration relative to other mediators present. Carboxypeptidase A can also affect angiotensin II level as well. Renin regulates the level of a molecule that becomes angiotensin II and can increase blood pressure this way.

Phospholipases, which help produce the molecule needed to make prostaglandins, leukotrienes and thromboxanes can contribute to either high or low blood pressure depending upon which molecule is made. Prostaglandin D2 (PGD2) is a vasodilator, lowering blood pressure; but its metabolite, 9a,11b-PGF2, increases blood pressure. (Author’s note: I personally believe this to be the reason for the rapid blood pressure fluctuations in mast cell patients, but do not have evidence to directly support this.) Thromboxane A2, a molecule related to prostaglandins and leukotrienes, increases blood pressure, as do leukotrienes.

Management of high blood pressure is complicated in mast cell patients by the interaction of common antihypertensives with mast cell activation. Beta blockers are contraindicated in mast cell patients because they interfere with epinephrine, both naturally produced and medicinally.  Use of beta blockers is a risk factor for fatal anaphylaxis.  Any patient on beta blockers that carries an epipen should also carry a glucagon pen, which can be administered prior to the epipen to increase efficacy.

ACE inhibitors interfere with angiotensin converting enzyme, which increases blood pressure through the angiotensin II pathway.  ACE inhibitors affect bradykinin levels, a mast cell mediator that is also mast cell activating.  For this reason, ACE inhibitors can increase mast cell reactivity and symptoms like angioedema.

Author’s note:  I extended this series to four posts to discuss heart failure in mast cell patients.  Following this series, I will be posting a series dedicated exclusively to Kounis Syndrome, including diagnosis and treatment.  Sit tight!


Kolck UW, et al. Cardiovascular symptoms in patients with systemic mast cell activation disease. Translation Research 2016; x:1-10.

Gonzalez-de-Olano D, et al. Mast cell-related disorders presenting with Kounis Syndrome. International Journal of Cardiology 2012: 161(1): 56-58.

Kennedy S, et al. Mast cells and vascular diseases. Pharmacology & Therapeutics 2013; 138: 53-65.


Prostaglandin E2, mast cells and asthma

In the mast cell community, we talk about prostaglandins a lot. Most of the time we are talking about prostaglandin D2, as it is well produced by mast cells. However, there are a number of other prostaglandins that can affect inflammation and disease processes.

Prostaglandin E2 has been inflammatory and anti-inflammatory effects in the body. It is the prostaglandin responsible for inducing fevers. It is also a vasodilator, which contributes in some models to swelling. It relaxes smooth muscle and interferes with release of norepinephrine. PGE2 can cause hyperalgesia, or exaggerated pain response, a hallmark of inflammation. It regulates blood pressure, body temperature, sleep-wake pattern, kidney function and peristalsis (movement through the GI tract), and intestinal secretion.

It activates T cells and favors development of certain types of T cells that participate in the allergic response. It also modulates B cell activity and allergic reactions. However, it makes other immune cells less active. PGE2 simulates bone resorption and is important in reproduction, softening the cervix and causing uterine contractions.

PGE2 has a number of interactions with mast cells. In mast cells from bone marrow or peritoneal cavity, it induces histamine, IL-6 and GM-CSF release. However, in mast cells from progenitor cells or in the lung, it decreases release of leukotrienes, TNF and histamine. PGE2 acts on mast cells to reduce expression of PGE receptors, EP2 and EP3. PGE2 can enhance IgE production by B cells but also interferes directly with mast cell degranulation stimulated by IgE.

Prostaglandin E2 has a very unusual relationship with allergic inflammation. In contrast to prostaglandin D2, which constricts the airway, PGE2 actually relaxes the smooth muscle and opens the airway. Importantly, PGE2 retains this ability regardless of the trigger for reactive airway – allergen, asthma or exercise. Curiously, it was observed early on to cause coughing.

An interesting fact is that administration of medications that interfere with COX-2 (like Celebrex or aspirin) can worsen airway function and increase inflammation. This is of particular note in asthma patients. It is thought that this may be due to reducing production of PGE2.



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

Rosa Torres, César Picado, Fernando de Mora. The PGE2–EP2–mast cell axis: An antiasthma mechanism. Molecular Immunology 63 (2015) 61–68

Daniel F. Legler, Markus Bruckner, Edith Uetz-von Allmen, Petra Krause. Prostaglandin E2 at new glance: Novel insights in functional diversity offer therapeutic chances. The International Journal of Biochemistry & Cell Biology 42 (2010) 198–201.

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.



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

Prostaglandins and leukotrienes

Prostaglandins are molecules that behave like hormones and are used for signaling between cells. They are produced by many cell types and tissues in the body.

To make prostaglandins, an enzyme called phospholipase A2 turns diacylglycerol into arachidonic acid (AA). All prostaglandins are derived from AA and this molecule is mentioned often in scientific literature about mast cells, as it is easier to detect AA than some prostaglandins. Once AA has been produced, one of two things happen: AA is either changed by the cyclooxygenase (COX) pathway into prostaglandins and thromboxanes or by the lipoxygenase (LO) pathway into leukotrienes.

Prostaglandins, thromboxanes and leukotrienes are all types of eicosanoids. Eicosanoid is another common word in mast cell literature, and in that context it usually refers to prostaglandins or leukotrienes.

To make prostaglandins from AA, cells use the enzymes COX-1 and COX-2. COX-1 produces regular low levels of prostaglandins, whereas COX-2 makes prostaglandins in response to inflammation. Other enzymes called prostaglandin synthases finish off making the prostaglandins into the right shapes. To make leukotrienes from AA, cells use the enzyme arachidonate 5-lipoxygenase.

There are a number of medications that interfere with the production of leukotrienes or prostaglandins by interfering with the enzymes that make them. This is generally regarded as a more effective way to treat symptoms from these products, rather than trying to block their action after they have been made.

Non steroidal anti-inflammatories (NSAIDs), of which there are dozens, interfere with the activity of both COX-1 and COX-2. Newer COX-2 inhibitors like Celebrex only inhibit COX-2. Vitamin D downregulates expression of COX-2. A chemical in St. John’s Wort is also a COX-1 inhibitor. Zileuton is a lipoxygenase inhibitor.