Research on Serotonin Levels in Autoimmunity

Absence of reuptake of serotonin influences susceptibility to clinical autoimmune disease and neuroantigen-specific interferon-gamma production in mouse EAE
HH Hofstetter,* R Mössner,† KP Lesch,† RA Linker,*‡ KV Toyka,* and R Gold*‡ (2005)

"These findings suggest a potential role of extracellular 5-HT homeostasis in the fine-tuning of neuroantigen-specific immune responses."


Sustained remission of rheumatoid arthritis with a specific serotonin reuptake inhibitor antidepressant: a case report and review of the literature

"In the present case, we see that treatment of co-morbid depression with an SSRI led to complete remission of arthritis in a 60-year-old individual. Postulated mechanisms through which antidepressants mediate this effect include their agonistic action on 5-HT2A receptors or inhibition of the signaling of Toll-like receptors that are responsible for mediating innate immunity. The relation between mediators of inflammation and biologic substrates of mood seem to be bidirectional."


Blood serotonin and joint pain in seropositive versus seronegative rheumatoid arthritis.
Sigvard Kopp and Per Alstergren
Department of Clinical Oral Physiology, Institute of Odontology, Karolinska Institutet, Box 4064, 141 04 Huddinge, Sweden.

"RESULTS: The patients with seropositive RA had higher serum (median = 1130 nmol/l) and plasma (55 nmol/l) levels of 5-HT than the healthy individuals (704 nmol/l, p = 0.044 and 23 nmol/l, p < 0.001, respectively), and higher plasma levels of 5-HT than the seronegative patients (14 nmol/l, p < 0.001)." Effect of Clonazepam on Raynaud's Phenomenon and Fingertip Ulcers in Scleroderma
Murat Colakoğlu, MD
Associate Professor in Nephrology, Departmen of Nephrology, School of Medicine, Pamukkale University, Denizli, Turkey
Veli Cobankara, MD
Associate Professor in Rheumatology, Department of Rheumatology, School of Medicine, Pamukkale University
Tekin Akpolat, MD

"Clonazepam, unlike many other benzodiazepines, appears to have serotonergic effects, which may contribute to its psychotropic and antimyoclonic properties. While the therapeutic action remains unclear, clonazepam's serotonergic effects may be responsible for the beneficial effect on Raynaud's phenomenon and fingertip ulcers.

Raynaud's phenomenon and erythromelalgia are both vascular acrosyndromes. Serotonin has been involved in the pathogenesis of both Raynaud's phenomenon and erythromelalgia."


Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis
A Kling1, M Seddighzadeh2, L Ärlestig3, L Alfredsson4,5, S Rantapää-Dahlqvist3, L Padyukov2
Accepted 1 November 2007

"In our study, genetic polymorphisms at the HTR2A gene are associated with susceptibility for RA, suggesting possible links between the serotonergic system and development of the disease."



Association between the use of serotonin receptor 2A–blocking antidepressants and joint disorders
Anders Kling1,*, Marit Danell-Boman1, Hans Stenlund2, Rune Dahlqvist1
Article first published online: 29 SEP 2009

"In the Swedish material, the 5-HT2A antagonists were 45 times more often reported to give joint ADRs when related to sales figures and compared with the selective serotonin reuptake inhibitors (SSRIs; P < 0.001). Joint disorders constituted 6.6% of the total number of reports of possible ADRs for the three 5-HT2A–blocking substances mianserin, mirtazapine, and nefazodone compared with 0.5% for the SSRIs (P < 0.001). In the WHO material, the joint disorders constituted 1.3% of all ADRs for the 5-HT2A–blocking antidepressants and 0.6% for the SSRIs (P < 0.001)." Ann Rheum Dis 2006;65:816-819 doi:10.1136/ard.2005.042473 Decreased density of serotonin 5-HT2A receptors in rheumatoid arthritis
A Kling1, S Rantapää-Dahlqvist2, H Stenlund3, T Mjörndal1

"The density of 5-HT2A serotonin receptors in patients with rheumatoid arthritis is markedly reduced. This could either reflect a difference involved in the susceptibility to the disease or be a secondary effect of the disease"

5-Hydroxytryptamine and tryptamine pathways in scleroderma
A. STACHOW, S. JABLONSKA, A. SKIENDZIELEWSKA (2006)

"These results suggest impaired transformation of serotonin into 5-hydroxyindoleacetic acid. A disproportionately high ratio of total indoles to indoleacetic acid suggests the presence of excess of tryptamine. The results of the study may indicate that in scleroderma metabolism of biogenic amines derived from tryptophan is abnormal, probably as a result of impaired activity of monoamine oxidase."


Intraplatelet and urinary serotonin concentrations in systemic lupus erythematosus with reference to its clinical manifestations
Kanai H, Tsuchida A, Yano S, Naruse T.
Third Department of Internal Medicine, Gunma University School of Medicine, Japan

"Active SLE showed a significantly higher urinary 5-HT concentration, 0.37 +/- 0.15 nmol/ml/mg Cr, than normal controls, 0.21 +/- 0.08 nmol/ml/mg Cr (p less than 0.01). Serial measurements of intraplatelet and urinary 5-HT levels in five patients with SLE revealed a significant correlation between clinical activity and intraplatelet and urinary 5-HT levels. "


Serum Factors Releasing Serotonin from Normal Platelets: Relation to the Manifestations of Systemic Lupus Erythematosus
MARK H. GINSBERG, M.D.; and MICHAEL O'MALLEY, B.S.

"In three patients with episodes of thrombocytopenia, increases in serotonin releasing activity temporally coincided with drops in platelet count. These data show that levels of circulating platelet serotonin releasing factor(s) vary in the course of systemic lupus erythematosus and these variations may be inversely related to the platelet count in particular patients."


Headache, Raynaud’s syndrome and serotonin receptor agonists in systemic lupus erythematosus


Analysis of 5HT3Ra gene expression by real time PCR in Systemic Lupus
Erythematosus (SLE) patients
Mohammad Sabery Anvar, Ghasem Ahangari, Mohiedin Jafari, Shahin Dokht Samangouei, Raheleh Torabi
,Mohammad Taghi Sadeghi Kohpaieh

"We found over expression of 5HT3Ra in patients in comparison with healthy individuals group. Interestingly, some nucleotide changes have been found in 5HT3Ra gene in patients but not found sequential nucleotide changes in healthy individuals group. This study supposed that over expression of 5HT3Ra gene in SLE patients lead to over activation of immune cells that derived from over stimulation of them from serotonin blood serum that finally lead to autoimmune reactions that terminated in SLE."

Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome.
Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Javors MA, Bowden CA.
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874.

Alteration of serotonin transporter density and activity in fibromyalgia
by Laura Bazzichi, Gino Giannaccini, Laura Betti, Giovanni Mascia, Laura Fabbrini,

The Expanded Biology of Serotonin
Annual Review of Medicine
Vol. 60: 355-366 (Volume publication date February 2009)
DOI: 10.1146/annurev.med.60.042307.110802

"Additionally, new work suggests that serotonin may regulate some processes, including platelet aggregation, by receptor-independent, transglutaminase-dependent covalent linkage to cellular proteins. We review this new “expanded serotonin biology” and discuss how drugs targeting specific serotonin receptors are beginning to help treat a wide range of diseases.'
Miles Berger,1 John A. Gray,1,2 and Bryan L. Roth


Ablation of Serotonin 5-HT2B Receptors in Mice Leads to Abnormal Cardiac Structure and Function
Circulation. 2001;103:2973-2979
doi: 10.1161/01.CIR.103.24.2973

"Conclusions—Mutation of 5-HT2B receptor leads to a cardiomyopathy without hypertrophy and a disruption of intercalated disks. 5-HT2B receptor is required for cytoskeleton assembly to membrane structures by its regulation of N-cadherin expression. These results constitute, for the first time, strong genetic evidence that serotonin, via the 5-HT2B receptor, regulates cardiac structure and function."
(Circulation. 2001;103:2973.)




Recent advances in understanding serotonin regulation of cardiovascular function
Francine Côté1, Cécile Fligny1, Yves Fromes2, Jacques Mallet1, , Guilan Vodjdani1

"Recent studies have provided evidence that, in the absence of peripheral serotonin synthesis, blood serotonin (which is almost exclusively stored in platelets) is markedly reduced, and that this drop leads to heart failure. This implies that the level of circulating serotonin is a key factor in maintaining normal cardiovascular activity. These findings offer new prospects for the use of serotonin in therapies for cardiovascular diseases."


Int J Cardiol. 1988 Jun;19(3):335-9.
Plasma free and intraplatelet serotonin in patients with Raynaud's phenomenon.

"Serotonin was significantly higher in plasma (P less than 0.005) and in platelets (P less than 0.005) from Raynaud's patients than from normal controls. Moreover, plasma circulating serotonin could differentiate primary from secondary Raynaud's phenomenon, with significantly higher levels (P less than 0.05) for patients with an underlying connective tissue disease. Our data indicate a role for serotonin in Raynaud's phenomenon."
Biondi ML, Marasini B, Bianchi E, Agostoni A.
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Scleroderma and L-tryptophan: a possible explanation of the eosinophilia-myalgia syndrome
SM Connolly, SR Quimby, WL Griffing, RK Winkelmann

"These findings confirm previous data that show altered tryptophan-kynurenine metabolism in some patients with scleroderma and fasciitis, particularly with tryptophan loading."

Relationship between Infection (Viral, Bacterial) and Serotonin

Rotavirus Stimulates Release of Serotonin (5-HT) from Human Enterochromaffin Cells and Activates Brain Structures Involved in Nausea and Vomiting
Marie Hagbom1#, Claudia Istrate1,2#¤a, David Engblom3, Thommie Karlsson4, Jesus Rodriguez-Diaz5¤b, Javier Buesa5, John A. Taylor6, Vesa-Matti Loitto4, Karl-Eric Magnusson4, Håkan Ahlman7, Ove Lundgren8, Lennart Svensson1*
1 Division of Molecular Virology, Medical Faculty, University of Linköping, Linköping, Sweden, 2 Unidade de Biologia Molecular, Centro de Malaria e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal, 3 Division of Cell Biology, Medical Faculty, University of Linköping, Linköping, Sweden, 4 Division of Medical Microbiology, Medical Faculty, University of Linköping, Linköping, Sweden, 5 Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain, 6 School of Biological Sciences, University of Auckland, Auckland, New Zealand, 7 Department of Surgery, University of Gothenburg, Gothenburg, Sweden, 8 Department of Physiology, University of Gothenburg, Gothenburg, Sweden

More research on Serotonin, Depression and Scleroderma

Commonly Used Antidepressants May Also Affect Human Immune System 2006

Depression may involve autoimmune attack on serotonin (5-HT) Dec 2011

"The incidence of anti-5-HT antibody activity was significantly higher in depressed patients (54.1%), and in particular in those with melancholia (82.9%), than in controls (5.7%)."

Biogenic amines derived from tryptophan in systemic and cutaneous scleroderma.
(PMID:84460)

"An increased T/IAA ratio seems to be of prognostic significance in scleroderma, suggesting an adverse course of the disease."

NeuroScience - Offers Urine Test for 5HT levels

How to lower serotonin levels naturally... (Livestrong)

Effect of antibiotics on D-serotonin-reactive structures

Balancing gut flora and the "second brain" without prescription medication

Cardiac fibrosis and Serotonin

Tryptophan Depletion and Mood Disorders


Tryptophan, serotonin, and aging This man is a genius (Ray Peat)

Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: Reduction by a selective serotonin reuptake inhibitor

Neurogenesis and Serotonin

Too much not too little serotonin may trigger depression

The Other Brain Also Deals With Many Woes
By HARRIET BROWN
Published: October 11, 2011

Serotonin Findings Cause Depression Rethink

Serotonin Syndrome

Think Twice: How the Gut's "Second Brain" Influences Mood and Well-Being

Serotonin and Gut/Esophageal Peristalsis (Important to Scleroderma Patients)
The effect of erythromycin on human esophageal motility is mediated by serotonin receptors.


Acute autoimmune encephalomyelitis in mice. II. Susceptibility is controlled by the combination of H-2 and histamine sensitization genes.

Compounds that induce autoimmunity in the Brown Norway rat sensitize mast cells for mediator release and interleukin-4 expression
David B. G. Oliveira1,*, Kathleen Gillespie1, Karen Wolfreys1, Peter W. Mathieson1, Faieza Qasim1, John W. Coleman2


Elevated Serotonin Levels in Autism: Association with the Major Histocompatibility Complex
Article first published online: 23 NOV 2005

Inhibition of Hypoglycemia-Induced Cortisol Secretion by the Serotonin Antagonist Cyproheptadine

Effect of the Serotonin Precursor, Tryptophan, on Pituitary Hormone Secretion
These effects are presumably mediated by conversion of tryptophan to serotonin within the central nervous system and suggest that serotonin is a potent inhibitor of hypothalamic CRF elaboration in man.

Effects of Selective Serotonin Reuptake Inhibitors on Thyroid Function in Depressed Patients with Primary Hypothyroidism or Normal Thyroid Function
Gisah Amaral de Carvalho, Saint-Clair Bahls, Anke Boeving, and Hans Graf. Thyroid. July 2009, 19(7): 691-697. doi:10.1089/thy.2008.0261.

Serotonin and its precursors as modulators of the immunological responsiveness in mice.

Association of erythromelalgia and Raynaud's disease responding to a serotonin reuptake inhibitor
1999, Vol. 10, No. 2 , Pages 141-144

Scleroderma treatment differs between experts and general rheumatologists
Janet E. Pope, Janine M. Ouimet, Adriana Krizova
"Erectile dysfunction (25–30) and depression (31–35) seem to be frequent problems in scleroderma, each with a substantial impact on patients, and this has been reported in the literature." = excess serotonin!!!

Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.
Psychosom Med. 2010 Nov;72(9):925-32. Epub 2010 Oct 14.

Serotonin and Scleroderma (Fibrosis)

Platelet-derived serotonin links vascular
disease and tissue fibrosis 2011

Modulation of bleomycin-induced lung fibrosis by serotonin receptor antagonists in mice
A. Fabre 1 , 2 , J. Marchal-Sommé 1 , S. Marchand-Adam 1 , 3 , C. Quesnel 1 , R. Borie 1 , M. Dehoux 1 , 4 , C. Ruffié 1 , J. Callebert 5 , J-M. Launay 5 , D. Hénin 2 , P. Soler 1 and B. Crestani 1 , 3

"Serotonin (5-hydroxytryptamine; 5-HT) is known to increase proliferation and collagen synthesis by fibroblasts. Two receptor subtypes, 5-HT2A and 5-HT2B, have been shown to play the most important roles in the lung. Serotonin antagonists promoted an antifibrotic environment by decreasing the lung mRNA levels of transforming growth factor-β1, connective growth factor and plasminogen activator inhibitor-1 mRNA... Interestingly, the 5-HT2B receptor was strongly expressed by fibroblasts in the fibroblastic foci in human idiopathic pulmonary fibrosis samples."

Treatment of Carcinoid Fibrosis

Positive data from Lexicon LX1032 Phase 2 study on carcinoid syndrome

Potaba ® Potassium P-Aminobenzoate, U.S.P.

Development of a Scleroderma-like Illness during Therapy with L-5-Hydroxytryptophan and Carbidopa

Our data and studies in the literature suggest that two factors may be important in the pathogenesis of some scleroderma-like illness: high plasma serotonin and the abnormality associated with elevated kynurenine. (N Engl J Med. 1980; 303:782–7.)


Depression, osteoporosis, serotonin and cell membrane viscosity between biology and philosophical anthropology


At the time it is shown that the viscosity of the platelet membrane is a general influencing factor for serotonin receptor uptake, a general principle governing the handling of serotonin itself is established with regard to its relations with the depressive disorder. It may also be involved, to a certain extent, in some pathologies that recognise serotonin changes; that is, scleroderma, inflammatory bowel disease, neuroinflammation, multiple sclerosis and osteoporosis.

The high incidence of depression, in these pathological conditions, leads us to consider a general phenomenological rule rather than a specific error in gene expression or loss of enzyme function. The viscosity of the membrane appears to be a concept more plausible than the fact that it is a phenomenon to which changes may contribute more general factors compared to the exclusivity of a gene expression error and/or an abnormality of enzyme function. The serotonin receptors and their subtypes, together with the modification of gene expression of transporters, represent a very complex and intriguing network. We must understand if it is possible to find a general and common rule to explain all the different molecular aspects of the serotonin pathways, tissue connections and responsibilities in its involvement in pathologies.

Raynaud's Phenomenon and Serotonin Reuptake Inhibitors

Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine

Plasma free and intraplatelet serotonin in patients with Raynaud's phenomenon

Management of Vasculopathy in Connective Tissue Disease

Handb Exp Pharmacol. 2007;(178):347-63.
A novel conditional knockout strategy applied to serotonin receptors.

The Serotonin Signaling System: From Basic Understanding To Drug Development for Functional GI Disorders
Michael D. Gershon⁎, , , Jan Tack‡
Department of Pathology & Cell Biology, Columbia University, College of Physicians and Surgeons, New York, New York

Doxycycline and Serotonin

Serotonin 5HT-1A receptor density in the brain of the spontaneously hypertensive rats
After doxycycline treatment, serotonin 5HT-1A extracellular domain receptor density was significantly increased in the treated SHRs (p<0.05). These results suggest that doxycycline can increase extracellular domain receptor density.

Many Benefits Of N-Acetyl Cysteine

Protective effect of n-acetylcysteine in a model of influenza infection in mice.
Ungheri D, Pisani C, Sanson G, Bertani A, Schioppacassi G, Delgado R, Sironi M, Ghezzi P.
Zambon Research, 20092 Bresso, Milan (2000)

N-Acetylcysteine: Multiple Clinical Applications
PAUL J. MILLEA, MD, MA, Department of Integrative Medicine, Mid-Atlantic Permanente Medical Group, P.C., Falls Church, Virginia
Am Fam Physician. 2009 Aug 1;80(3):265-269.

High-Dose N-Acetylcysteine Therapy for Novel H1N1 Influenza Pneumonia
Kang Yiu Lai, MRCP; Wing Yiu Ng, MRCP; Pik Kei Osburga Chan, MRCP; Kit Fai Wong, MD, MRCP; and Fanny Cheng, MRCP (2009)

Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro.
Riise GC, Qvarfordt I, Larsson S, Eliasson V, Andersson BA.
Department of Pulmonary Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. gerdt.riise@hjl.gu.se (2000)

Antifibrotic Effects of Antioxidant N-Acetylcysteine in a Mouse Model of Human Hypertrophic Cardiomyopathy Mutation
Ali J. Marian, MD, FACC*, Vinitha Senthil, PhD, Suet N. Chen, MS and Raffaella Lombardi, MD
Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas (2005)

High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis
Rabindra Tirouvanziam,*† Carol K. Conrad,‡ Teodoro Bottiglieri,§ Leonore A. Herzenberg,* Richard B. Moss,‡ and Leonard A. Herzenberg*†
*Departments of Genetics and
‡Pediatrics, Stanford University School of Medicine, Stanford, CA 94305; and
§Institute of Metabolic Disease, Baylor University, Dallas, TX 75226 (2006)

High-Dose Acetylcysteine in Idiopathic Pulmonary Fibrosis
Maurits Demedts, M.D., Juergen Behr, M.D., Roland Buhl, M.D., Ulrich Costabel, M.D., P.N., Richard Dekhuijzen, M.D., Henk M. Jansen, M.D., William MacNee, M.D., Michiel Thomeer, M.D., Benoit Wallaert, M.D., François Laurent, M.D., Andrew G. Nicholson, M.D., Eric K. Verbeken, M.D., Johny Verschakelen, M.D., Christopher D.R. Flower, M.D., Frédérique Capron, M.D., Stefano Petruzzelli, M.D., Paul De Vuyst, M.D., Jules M.M. van den Bosch, M.D., Eulogio Rodriguez-Becerra, M.D., Giuseppina Corvasce, Ph.D., Ida Lankhorst, M.D., Marco Sardina, M.D., and Mauro Montanari, Ph.D. for the IFIGENIA Study Group
N Engl J Med 2005;

N-acetylcysteine improves the clinical conditions of mustard gas-exposed patients with normal pulmonary function test.
Ghanei M, Shohrati M, Jafari M, Ghaderi S, Alaeddini F, Aslani J.
Research Center of Chemical Injuries, Baqiyatallah University of Medical Sciences, Tehran, Iran. (2008)

Health Benefits of Saffron

Saffron Shows Promise In Preventing Liver Cancer

Saffron: A potential candidate for a novel anticancer drug against hepatocellular carcinoma.

Saffron Valued for Supporting Liver Health

Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: A pilot double-blind randomized trial [ISRCTN45683816]

Studies Connecting Autoimmunity to Viral and Bacterial Infection

Infections and autoimmunity: the multifaceted relationship.
Sfriso P, Ghirardello A, Botsios C, Tonon M, Zen M, Bassi N, Bassetto F, Doria A.
Department of Clinical and Experimental Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. (2009)

Infections and autoimmunity: a panorama.
Pordeus V, Szyper-Kravitz M, Levy RA, Vaz NM, Shoenfeld Y.
Clinical Research, Pro Cardiaco Hospital Research Center-PROCEP, Rio de Janeiro, Brazil. (2008)

From infection to autoimmunity.
Fairweather D, Kaya Z, Shellam GR, Lawson CM, Rose NR.
The Department of Pathology and The W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins University, Baltimore, Maryland, USA. (2001)

Infection, vaccines and other environmental triggers of autoimmunity.
Molina V, Shoenfeld Y.
Department of Medicine B and The Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel. (2005)


Infections and autoimmune diseases.
Bach JF.
Laboratoire d'Immunologie, Hôpital Necker, 161 rue de Sèvres, 75743 Paris Cedex 15, France. bach@necker.fr
(This abstract is really thorough and fascinating!)

Infection in systemic lupus erythematosus: friend or foe?
Francis L, Perl A.
Division of Rheumatology, Department of Medicine State University of New York, College of Medicine 750 East Adams Street Syracuse, New York 13210, USA

Can infections protect against autoimmunity?
Gaisford W, Cooke A.
Department of Pathology, University of Cambridge, Cambridge, UK. (2009)

Induction, exacerbation and inhibition of allergic and autoimmune diseases by infection.
Kamradt T, Göggel R, Erb KJ.
Institut für Immunologie, Klinikum der Friedrich Schiller Universität Jena, 07740 Jena, Germany. (2005)


Regulation of type 1 diabetes, tuberculosis, and asthma by parasites.
Liu Z, Liu Q, Bleich D, Salgame P, Gause WC.
Source
Department of Medicine, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. (2010)


Parasitic worms and inflammatory diseases.
Zaccone P, Fehervari Z, Phillips JM, Dunne DW, Cooke A.
Department of Pathology, Tennis Court Road, Cambridge, UK. (2006)