Take home points: November 2015

Immunoglobulin free light chains: A possible link between autoimmune disease and mast cell activation

  • Light chains are part of antibodies that fight infections and responds to allergens
  • Free light chains are pieces of antibodies that broke off and do not work as antibodies
  • Elevation of immunoglobulin free light chains has been linked to many diseases, including lupus, rheumatoid arthritis, inflammatory bowel disease and food allergy
  • Free light chains correlate with symptom severity and flares in some conditions
  • Free light chains may be able to activate mast cells without IgE involvement
  • Free light chains may be the link between mast cell activation and autoimmune disease

Explain the tests: Complete blood count (CB) with differential and platelets (Part One)

  • A complete blood count (CBC) counts white blood cells, red blood cells and platelets in blood
  • It also looks at the shape, size and variation in size of cells

Explain the tests: Complete blood count (CBC) – Low red cell count (Part two)

  • Mature red blood cells live in the blood for 100-120 days
  • Hemolysis is when red blood cells burst and a little bit of hemolysis is normal
  • Red blood cells transport oxygen from lungs to tissues
  • Red blood cells have hemoglobin inside them
  • Hemoglobin is a protein with iron in the middle and it carries oxygen
  • Low red blood cell count or hemoglobin is called anemia
  • Red blood cell count can be low for several reasons, including nutritional deficiency and production dysregulation in bone marrow
  • Mast cell patients often suffer from anemia of chronic inflammation, which can cause low red count
  • Patients with inflammatory bowel disease can have low red count due to bleeding
  • Swelling of spleen can cause low red count

Take home points: October 2015

Childhood mastocytosis: Update

  • Cutaneous mastocytosis in children is the most common form of mastocytosis
  • True systemic mastocytosis is very rare in children
  • An NIH study of 105 children found 30-65% improved over time
  • Elevated baseline tryptase level and organ swelling were good indicators of SM
  • Serum tryptase should be measured every 6-12 months
  • Children with swelling of both liver and spleen were positive for CKIT D816V mutation
  • Swelling of liver and spleen together was linked to disease persisting into adulthood
  • Most children with UP with skin and minor GI issues had normal tryptase
  • Diffuse cutaneous mastocytosis patients had a much higher average tryptase but no organ swelling
  • Serum tryptase and IgE were inversely related (high tryptase with low IgE, low tryptase with high IgE)

Chronic mast cell leukemia: a new variant of systemic mastocytosis

  • Mast cell leukemia (MCL) has a significantly shortened lifespan
  • Usually over 20% of nucleated cells in bone marrow are atypical mast cells
  • Mast cells are present in large quantities on the blood
  • Cases where less than 10% of white blood cells in blood are mast cells are called aleukemic variant MCL
  • Cases where over 20% of nucleated cells in bone marrow are mature mast cells are called chronic MCL
  • Chronic MCL patients do not have any C findings (the clinical markers for SM patients associated with very aggressive disease)
  • Chronic MCL patients have stable disease state but can progress to acute MCL at any time
  • Mediator release symptoms are more common in chronic MCL than acute MCL
  • Acute MCL is marked by immature CD25+ mast cells
  • Acute MCL patients do have C findings (the clinical markers for SM patients associated with very aggressive disease)
  • Acute MCL has a very short survival time, usually less than a year

Take home points: August 2015

Gastroparesis: Part 1

  • GP is a condition in which stomach contents do not move into the small intestine in an appropriate time frame without an obvious anatomical reason
  • GP patients can have severe symptoms, including nausea, vomiting, abdominal pain and bloating
  • GP can be episodic or chronic
  • The degree of gastric emptying delay does not impact symptom severity
  • GP may affect up to 2% of the population
  • GP is increasing over the last twenty years with no clear reason as to why
  • Cisapride is effective for treating GP but was removed from the market
  • GP symptoms are generic and make the cause hard to identify
  • Idiopathic GP has no clear cause and affects up to 1/3 of GP patients

Gastroparesis: Treatment (Part 2)

  • Treating dehydration and electrolyte and nutritional deficiencies are key to initial GP management
  • 64% of GP patients do not consume enough daily calories
  • Vitamins A, B6, C and K, iron, potassium and zinc are often deficient in GP patients
  • Small meals with low fat and fiber are recommended
  • Liquids or blended solids often empty normally from stomach
  • Feeding tubes may be placed if malnutrition is significant
  • Metoclopramide is approved for GP but use longer than twelve weeks carries risks like dystonia
  • Domperidone is not approved in US for GP but can be imported through a special FDA program for GP
  • Medications to increase gastric motility, like erythromycin, are often used
  • Medications for nausea and vomiting are common, such as ondansetron, scopolamine, draonabinol and tricyclic antidepressions
  • Nortriptyline and desipramine are tricyclics of choice as amitryptline can cause delayed gastric emptying
  • Opiates can induce GP so meds like gabapentin, tramadol, tapentadol, pregabalin and nortriptyline are preferred for abdominal pain
  • Botox injection into pyloric sphincter can increase gastric emptying but doesn’t always improve symptoms
  • Acupuncture and gastric pacemaker are also options

Gastroparesis: Diabetes and gastroparesis (Part 3)

  • 40% of patients with type I diabetes have delayed gastric emptying
  • 20% of patients with type II diabetes have delayed gastric emptying
  • In 2004, 26.7% of GP patients had diabetes
  • Diabetic patients with GP are more likely to have nausa and vomiting as predominant symptoms
  • GP can hinder effective blood sugar management
  • High blood sugar is associated with GP and vagus nerve damage
  • Gastric electric stimulation (gastric pacemaker) works better when GP is caused by diabetes than GP from other causes
  • Effective GP management improves blood sugar management and A1C level

Gastroparesis: Post-surgical gastroparesis (Part Four)

  • Surgery is a common trigger for GP
  • Surgeries that manipulate the stomach are more associated with GP, like gastrectomy, fundoplication or weight loss surgery
  • Gastric inflammation associated with surgery inhibits GI motility
  • 7.2% of GP cases occur after gastrectomy or fundoplication
  • Nissen fundoplication is the most common cause of post-surgical GP
  • A follow up surgery after Nissen fundoplication can sometimes reverse GP
  • Surgeries that don’t manipulate the stomach can also cause GP, like removal of esophagus, lung transplant, and liver surgery

Gastroparesis: Less common causes (Part Five)

  • Parkinson disease, multiple sclerosis, muscular dystrophy, myopathy, scleroderma, Sjogrens, polymyositis and stroke can all cause GP.
  • 10.8% of GP cases are associated with connective tissue disorder
  • Pseudo obstruction syndromes and autonomic neuropathy can occur concurrently with GP
  • Viral infections can cause acute GP that usually resolves within a year
  • Spinal cord injury, hypothyroidism, hyperparathyroidism, Addison’s disease and use of opiates or anticholinergics can contribute to GP
  • GP occurs disproportionately in people who have had their gallbladders removed
    • Often, GP does not immediately follow gallbladder removal but can present months or years later
    • Gallbladder removal is also associated with conditions that can occur with GP such as chronic fatigue syndrome, fibromyalgia, depression and anxiety
    • GP patients who have had gallbladders removed are usually older women who are overweight despite not coming enough calories

Take home points: September 2015

Naturally occurring mast cell stabilizers: Part 1

Naturally occurring mast cell stabilizers: Part 2

Naturally occurring mast cell stabilizers: Part 3

Naturally occurring mast cell stabilizers: Part 4

Amentoflavone Ginkgo biloba, St. John’s Wort Decreases histamine release
Artekeiskeanol A Artemisa keiskeana May treat arthritis

Decreases mast cell degranulation

Decreases production of IL-13 and TNF

Curcimin Turmeric Decreases degranulation

Decreases production of IL-4 and TNF

Ellagic acid Strawberries, raspberries, pomegranate, walnuts Suppresses IgE activation

Decreases release of histamine, TNF, IL-6

Emodin Rhubarb, frangula bark Decreases IgE degranulation

Decreases IgE triggered production of TNF, PGD2, LTC4

Decreases secretion of TNF and IL-6

Epigallocatechin gallate White and green teas, apples, onions, hazelnuts Decreases degranulation

Decreases LTC4 secretion

Fisetin Apples, onions, persimmon, strawberries, cucumber Decreases IgE degranulation

Decreased IgE triggered histamine release

Decreases production of IL-1b, IL-6, IL-8 and TNF

Decreased action of NF-kB, decreased mediator production

Furanocoumarin from Angelica dahurica Angelica dahurica Inhibits COX-2 and 5-LO, decreasing production of prostaglandins and LTC4
Genistein Genista tinctoria Decreases IgE degranulation

Decreases histamine release

Nature tyrosine kinase inhibitor

Ginkgetin Gingko biloba Inhibits COX-2 and 5-LO, inhibiting production of prostaglandins and leukotrienes
Gnetin H Paeonia aneomala Resveratrol derived polymer

Decreases mast cell degranulation

Effective at lower dose than reservatrol

Decreases histamine secretion

Decreases production of TNF, IL-4, COX-2 and PGE2

Homoisoflavonone Cremastra appendiculata Inhibits COX-2 and 5-LO, inhibiting production of prostaglandins and leukotrienes

Decreases IgE triggered production of TNF and IL-6

Honokiol Magnolia obovata Suppresses allergic response and basophil activation
Hydroxytyrosol Olive oil, olive leaves Inhibited activation of mast cells at high concentration
Hypothemycin Hypomyces mushrooms Interfere with activation of CKIT and IgE receptors, inhibiting mast cell activation


Decreases production of IL-4

Kaempferol Potatoes, squash, cucumbers, peaches, Aloe versa Decreases IgE degranulation

Decreased IgE triggered histamine release

Affects estrogen signaling

Luteolin Celery, carrots, chamomile tea Prophylactic use of luteolin suppresses activation of mast cells and T cells

Decreases IgE degranulation

Decreases production of mediators

Magnolol Magnolia obovata Suppresses allergic response and basophil activation
Morin Osage orange, guava Decreases mast cell degranulation

Decreases IgE activation

Myricetin Walnuts, onions, red grapes Decreases IgE degranulation

Decreased IgE triggered histamine release

Decreases production of IL-6 and TNF

Decreased action of NF-kB, decreased mediator production

Polydatin Resveratrol precursor

Makes small intestine mucosa less “leaky” and inhibited allergic reaction in intestines

Decreases degranulation by up to 65%

Decreases histamine in intestinal mucosa and serum

Decreases production of IL-4

Quercetin Red onion, sweet potato, kale Inhibits production of histamine, prostaglandins, leukotrienes, IL-1b, IL-6, IL-8 and TNF
Resveratrol Grapes, raspberries, blueberries, peanuts Directly interferes with degranulation

Decreases production of TNF, IL-6 and IL-8

Rottlerin Mallotus philippensis Decreases degranulation of airway mast cells

Decreases histamine release

Suppresses IgE activation

Rutin Decreases IgE degranulation

Decreased IgE triggered histamine release

Decreases production of IL-1b, IL-6, IL-8 and TNF

Decreased action of NF-kB, decreased mediator production

Scopoletin Stinging nettle, Japanese belladonna, chicory, passion flower Decreases production of TNF, IL-6, IL-8

Inhibits NF-kB, affecting mediator production

Selinidin Angelia keiskei Inhibits IgE degranulation

Decreases production of LTC4 and TNF

Substance Source Function
Thunberginol A Hydrangeae macrophylla Decreases histamine release

Decreases production of TNF and IL-4

Thunberginol B Hydrangeae macrophylla Decreases degranulation from IgE or other sources

Decreases IgE triggered production of IL-2, IL-3, IL-4, IL-13, TNF and GM-CSF

Xanthones from purple mangosteen Garcinia mangostana Decreases release of histamine, PGD2, LTC4 and IL-6


Role of sex hormones in hereditary angioedema

Gastroparesis: Autonomic nervous system and vagus nerve (Part Six)

  • ANS controls many involuntary functions including digestion and therefore gastric emptying
  • The vagus nerve coordinates gastric motility
  • ANS dysfunction inhibits digestion and motility
  • GP is common in patients with ANS conditions, like POTS
  • Treatment of autonomic dysfunction (as in POTS) can sometimes improve GP
  • Damage to the vagus nerve can cause liquids to move rapidly out of the stomach while solids are retained
  • Surgery and high blood sugar can damage the vagus nerve
  • In GP patients, nerve cells are not shaped correctly
  • 83% of GP patients have abnormalities in their stomach biopsies

Gastroparesis: Idiopathic gastroparesis (Part Seven)

  • 35-67% of GP cases are idiopathic (IGP)
  • IGP affects three times more women than men, especially young and middle-aged women
  • IGP is more likely in young women who are overweight or obese
  • Moderate to severe abdominal pain was more frequent in IGP than other types
  • Nausea, abdominal pain, vomiting, bloating and feeling full are common in IGP
  • Medications that may be helpful but need investigation include sildenafil, paroxetine, cisapride, tegaserod, clonidine and buspirone

Calling all MastAttackers

For reasons I would rather not get into, the past few weeks have been very stressful. On top of this, summer is always hard for me because of the heat. I have to use my available resources to first keep up with work and other responsibilities with the blog coming after.

The silver lining to this situation is that it has forced me to realize that I absolutely cannot keep doing this the way I have been doing. It is not safe for me. It has forced me to think about what tasks can be delegated and the best way to educate mast cell patients and providers as a group to lessen the burden on me and others like me in various organizations.

I’m taking a few weeks off to come back in August with a stronger team so that MastAttack is not synonymous with me. I will continue to produce content, answer questions and interact with patients, but additional help in some other areas will make me better able to serve this community.

A number of people have reached out to ask how they can help. I have the following needs:

• Technical blog posts need to be edited to include bulleted summaries without jargon at the top of each post.

• Frequently asked questions need to be compiled with answers and posted on the blog as a page. These answers are assuredly on the blog already, it’s a matter of putting it all in one place.

• Older posts needs to be curated to ensure that the information there is still accurate. Wherever possible, any information from older posts that is still relevant should be incorporated into newer posts and the older posts removed.

• Redundant posts need to be combined and organized.

• Any research for requested posts would be really helpful. You do not need to have a science background for this, but I need to feel confident that you have a reasonable understanding of mast cell biology.

• Research or posts on conditions that commonly occur with mast cell disease. Again, you do not need to have a science background for this, but I need to feel confident that you have a reasonable understanding of mast cell biology.

• Questions for me need to be prioritized. For questions that have already been answered somewhere on the blog, the person should be directed to the appropriate post.

• Suggested reading lists need to be generated for the blog to ensure that the reader reads posts that describe more entry level concepts prior to reading posts that describe more complex concepts.

• Messages and emails describing complex cases asking for my opinion need to be distilled down into shorter, more digestible information. The biggest reason it takes me forever to respond to emails like this is that I have to absorb four pages of information and then think about it before I respond. I have to think about exactly how I want to do this because I understand patients may be uncomfortable with someone else reading these messages, so don’t worry about it yet. I think I could set up a separate email for that or maybe a form that shows how to structure information.

• The Master Index and subpages need to be updated as newer posts are published.

• Monthly summaries need to be updated as newer posts are published.
If you are interested in helping, or have other suggestions for how to improve efficiency, please email me at Lisa.Klimas@gmail.com. I’m really excited about the future possibilities for MastAttack.


Take home points: July 2015

Mast cell interactions with B and T cells
• Mast cells communicate with other cells by:
o Releasing chemicals to tell another cell to do something
o Other cells releasing chemicals to tell mast cells to do something
o Moving right up against other cells, which allows the cells to “talk”
• B cells are white blood cells that make antibodies and protect against infections.
o Mast cells can tell B cells to make IgE, an allergy antibody.
o When mast cells touch B cells, the mast cells can release IL-6 which tells B cells to live longer.
o Mast cells can tell B cells to make IgA, an antibody.
• T cells are white blood cells that have many functions.
o T cells and mast cells are found close together in many inflammatory conditions, like ulcerative colitis.
o Activated T cells can activate mast cells.
o Mast cells can tell T cells to proliferate and produce inflammatory molecules.
o A kind of T cell called Treg (T reg, like in regulatory) cells can make mast cells harder to activate and interfere with degranulation.

Mast cells in kidney disease
• Kidney disease is often not identified until 60-70% of functional kidney cells have been damaged beyond repair.
• Mast cells are rare in healthy kidneys.
o Damaged kidneys can have up to 60x the normal amount of mast cells.
o Mast cell count is not related to disease severity.
• Atopic disease, like atopic dermatitis and allergic asthma, is linked to idiopathic nephrotic disease, kidney disease of unknown origin.
o The nephrotic disease and atopic disease could be manifestations of the same overarching condition.
o In patients with both, IgE levels are high.
• Tryptase is elevated in some patients with kidney damage.
• Mast cells are responsible for bringing other inflammatory cells to the damaged kidney.
• Mast cells can cause fibrosis in kidneys.
• In some roles, mast cells can protect kidneys from damage.

Regulation of mast cells by IgE and stem cell factor (SCF)
• Mast cells are mostly regulated in two ways
• IgE binds to the IgE receptor (FceRI) on mast cells and activates them
o Activation by IgE results in degranulation and secretion of mediators
o IgE induces mediator release by affecting the amount of calcium inside mast cells
• Stem cell factor (SCF) binds to the CKIT receptor on mast cells and tells them to stay alive
o SCF also increases degranulation and production of cytokines
o SCF helps mast cells to adhere to other cells

Mast cells in vascular disease: Part 3
• Mast cells are involved in the formation and growth of aneurysms
• Activated mast cell populations are increased in vessels that rupture
• Chymase, a mast cell mediator, can degrade vessels and increase risk of rupture
• Leukotrienes contribute to aneurysm formation

Patient questions: Is mast cell disease autoimmune?

Autoimmune disease is when your body has an abnormal immune response to something that is a normal part of the body. There are more than eighty currently identified autoimmune diseases and they affect a significant population worldwide. At least 2% of women are estimated to have at least one autoimmune condition. Multiple sclerosis, rheumatoid arthritis and lupus are examples of autoimmune disease. Autoimmune diseases can affect small areas or multiple organs or targets throughout the body.

There are a number of possible causes of autoimmune disease. Some well supported theories include:
1. Molecular mimicry. This occurs when the body is exposed to an external danger and direct antibodies and immune defense against this danger. However, once the danger has been resolved, the antibodies and immune defense are directed toward damaging some normal part of the body that by happenstance looks like the dangerous thing. A classic example of this is development of rheumatic fever, PANDAS and other complications after a Streptococcus infection. The body makes antibodies to fight Strep, the Strep is killed and infection resolved, but the antibodies then attack things in the body that look like strep to the antibodies.
2. Genetic predisposition. Mutations and improper expression of genes that mediate tolerance, like HLA genes, can result in autoimmune disease. In these patients, these anomalies cause the body to fail to recognize itself as “safe”.
3. Cryptic determinants. This refers to the situation in which a hidden part of a normal structure in the body is not usually “seen” by the rest of the body. When that hidden part is exposed to the rest of the body, the immune system does not recognize it and attacks it, thinking it is dangerous. I imagine this as a waterway in a year of drought. A river has many small black rocks on the bottom. When the water is high, like most years, you cannot see these rocks. In a year of drought, the water level drops and you can the black rocks on the bottom. They were always a natural part of the riverbed, and they were always there, you just couldn’t see them. This can happen inside the body too. Sometimes your immune system sees things that were always there but not seen by it before.

The key feature unifying autoimmune diseases is that the immune system directly targets a part of the body that is normal and healthy. In lupus, the body makes antibodies that target the DNA inside our cells, which is not just normal but critically important to survival. It doesn’t target defective DNA, it targets regular old, keeps us alive, DNA.

Mast cell diseases are not autoimmune diseases. Mast cell diseases are not directly their attacks to a normal, healthy part of the body. In mast cell disease, mast cells are dysregulated and behave inappropriately. While this can damage parts of the body, this damage occurs due to the general inflammatory environment rather than because mast cells specifically targeted those parts of the body. Aberrant mast cells aren’t saying, “Quick, there’s an intruder in the liver! Let’s go get them!” when it’s just your regular liver hanging out. They are just so activated that mediator release could damage some cells in the liver, and in other places at the same time. The mast cell activation does not specifically target the liver in this scenario.

A confusing aspect of mast cell disease is that MCAS can occur secondary to autoimmune disease and many MCAS patients have autoimmune disease. In this patient population, the MCAS is probably induced by the inflammation caused by the autoimmune disease. Even still, while the primary autoimmune disease targets specific parts of the body, MCAS does not target specific parts of the body to attempt to destroy them.

Interplay between mast cells and hormones: Part 5 of 8

Hormone Location released Major functions Interaction with mast cells Reference
Inhibin Testes, ovaries, placenta, pituitary Inhibits production of FSH No known interaction with mast cells
Insulin Pancreas Promotes transfer of glucose from blood to liver and muscle

Promotes production of glycogen in liver

Promotes liberation of glucose stores in liver

Increases growth and survival of mast cells

Increases degranulation and mediator release

Lessmann E, et al. Insulin and insulin-like growth factor-1 promote mast cell survival via activation of the phosphatidylinositol-3-kinase pathway. Experimental Hematology 2006: 34(11), 1532-1541.
Insulin like growth factor Liver Modulates cell growth and development

Behaves like insulin

Increases growth and survival of mast cells

Increases degranulation and mediator release

Lessmann E, et al. Insulin and insulin-like growth factor-1 promote mast cell survival via activation of the phosphatidylinositol-3-kinase pathway. Experimental Hematology 2006: 34(11), 1532-1541.
Leptin Adipose tissue Decrease of appetite Activates inflammatory cells and T cell responses

Increases production of TNF, IL-2 and IL-6

Decreases mediator production due to activation of IgE receptor

Suppresses secretion of ghrelin

Taildeman J, et al. Human mast cells express leptin and leptin receptors. Histochem Cell Biol 2009: 131(6), 703-711.
Luteinizing hormone (LH) Pituitary Stimulates ovulation and formation of corpus luteum

Stimulates testosterone production

Histamine decreases LH release by acting at H1 receptor.

Histamine increases release of luteinizing hormone releasing hormone (LHRH), also by acting at H1 receptor.

Miayke A, et al. Involvement of H1 histamine receptor in basal and estrogen-stimulated luteinizing hormone-releasing hormone secretion in rats in vitro. Neuroendocrinology 1987: 45(3), 191-196.

Pontiroli AE, et al. The effect of histamine and H1 and H2 receptors on prolactin and luteinizing hormone release in humans: sex differences and the role of stress. J Clin Endocrinol Metab 1981: 52(5), 924-928.

Melanocyte stimulating hormone (MSH) Pituitary Stimulates melanin production and release

Increases during pregnancy

MSH can induce apoptosis in mast cells

Dose dependent increase in histamine relief, but not in IL-1, IL-6, IL-8, TGFb or TNF

Sarkar A, et al. alpha-Melanocyte-stimulating hormone induces cell death in mast cells: involvement of NF-kappaB. FEBS Lett 2003: 549(1-3), 87-93.

Grutzkau A, et al. alpha-Melanocyte stimulating hormone acts as a selective inducer of secretory functions in human mast cells. Biochem Biophys Res Commun 2000: 278(1), 14-19.

Melatonin Pineal gland, immune system Induces sleep and lowers body temperature Mast cells produce and release melatonin regardless of activation state Maldonado MD, et al. Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation. Pharmacol Res 2010: 62(3), 282-287.


Interplay between mast cells and hormones: Part 4 of 8

Hormone Location released Major functions Interaction with mast cells Reference
Ghrelin Stomach, jejunum, duodenum, colon, brain, lungs, liver, adipose tissue, placenta, lymphatic system Stimulate appetite

Can cross BBB

Induced mast cell degranulation

Dose dependently induced histamine release

Inhibits many inflammatory molecules, like TNF, IL-8, MCP-1, IL-1b, IL-6, CRP, IL-12, VCAM-1, MMP2, MMP9, GM-CSF and IL-17

Opposes action of leptin, a mast cell mediator

Level is increased by lack of sleep, promoting excessive hunger.

Hirayama T, et al. Ghrelin and obestatin promote the allergic action in rat peritoneal mast cells as basic secretagogues. Peptides 2010: 31(11), 2109-2113.

Baatar D, et al. The effects of ghrelin on inflammation and the immune system. Molecular and Cellular Endocrinology 2011: 340(1), 44-58.

Glucagon Pancreas Regulates amount of available glucose

Triggers breakdown of glycogen and production of glucose in liver, raising blood sugar

Released when blood sugar is too low

Can increase level of cAMP in myocardium to overcome effect of beta blockers

Anecdotal reports that glucagon may be able to relax esophagus sphincter to pass impacted food



In anaphylaxis patients on beta blockers, glucagon can be used to reduce resistance to epinephrine and increase blood pressure

May be considered to treat Kounis Syndrome where epinephrine is contraindicated

Histamine H3 receptor may regulate glucagon release from pancreas


Nakamura T, et al. Role of histamine H3 receptor in glucagon secreting aTC1.6 cells. FEBS Open Bio 2015: 5, 36-41.

Thomas M, Crawford I. Glucagon infusion in refractory anaphylactic shock in patients on beta blockers. Emerg Med J 2005: 22, 272-276.

Glucagon-like peptide 1 (GLP-1) Small intestine Increases release of insulin and nausea

Decreases release of glucagon, desire to eat and amount of food consumed

Increases anxiety


Possible relationship   between GLP-1 and histamine in the brain, but still unclear

GLP-1 level is modulated by leptin, a mast cell mediator Increases ACTH and cortisol

Gotoh K, et al. Glucagon-like peptide-1, corticotropin-releasing hormone, and hypothalamic neuronal histamine interact in the leptin-signaling pathway to regulate feeding behavior. FASEB J 2005: 19(9), 1131-1133.
Gonadotropin releasing hormone Hypothalamus Stimulate FSH and LH release from pituitary

Part of HPG axis

Drive secondary sex characteristics

Regulate sex hormone release

Histamine induces GnRH release in some studies Noris G, et al. Histamine directly stimulates gonadotropin-releasing hormone secretion from GT1-1 cells via H1 receptors coupled to phosphoinositide hydrolysis. Endrocrinology 1995: 136(7), 2967-2974.
Growth hormone releasing hormone Hypothalamus Stimulate growth hormone release from pituitary

Regulates bone growth

Regulates metabolism of proteins, carbohydrates and lipids

Induces mast cell degranulation and release of serotonin and histamine, causing low blood pressure Macia RA, et al. Hypotension induced by growth hormone releasing peptide is mediated by mast cell serotonin release in the rat. Toxicology and Applied Pharmacology 1990: 104(3), 403-410.
Hepcidin Liver Decreases iron absorption in intestines

Decreases iron release by macrophages

Chronic inflammation causes elevated hepcidin, making iron less available. This is called anemia of chronic inflammation. Weiss G. Anemia of chronic disorders: new diagnostic tools and new treatment strategies. Seminars in Hematology 2015: 52(4), 313-320.
Human chorionic gonadotropin (HCG) Placenta Maintains hormone release in ovaries during pregnancy

Inhibition of immune defense against fetus

Not known to directly affect mast cell activation or histamine release Schumacher A, et al. Endocrine factors modulating immune responses in pregnancy. Front Immunol 2014: 5, 196.