Plasma Histamine Levels Research Articles

Adhesion molecules in experimental peanut allergy

Methods Peanut allergy was induced in mice on the C57Bl/6 background (IA) with 4 weekly oral gavage feedings of peanut protein and cholera toxin. After a two-week rest period, sensitized animals were challenged by intraperitoneal injection with crude peanut extract (CPE) and monitored for anaphylaxis. Clinical indicators of peanut allergy include decreased body temperature, scratching, swollen eyes, decreased movement and responsiveness, and moribund condition. We evaluated plasma histamine, total IgE, peanut-specific IgE, and peritoneal albumin levels as in vivo indicators of mast cell degranulation and vascular permeability. Targeted genes and phenotypes

Quercetin effectively quells peanut-induced anaphylactic reactions in the peanut sensitized rats.

Peanut allergy is the major leading cause of fatal or life-threatening anaphylactic reactions to foods. At present, there is no remedy for this condition. The applied pharmaceutical cares are merely palliative, while their deleterious side effects have already been established. Hence, many sufferers search for complementary and alternative medicines. A versatile-, "flavonol" subgroup-member of the flavonoid family, quercetin, is of paramount interest to investigators. In this study the effects of quercetin on peanut-induced anaphylactic reactions were investigated in a rat model of peanut allergy. Wistar rats were sensitized with crude peanut extract in the presence of Cholera toxin and Aluminium hydroxide. Sensitized rats were then allotted into three groups; Positive control, Quercetin-treatment and Sham, (n=7, each). Naive rats (n=7) served as negative controls. One week post-sensitization period, the rats in treatment group were treated with quercetin at a dose of 50 mg/kg(Body Weight)/mL Di-methyl-sulfoxide 5%/rat, over a period of four weeks. Subsequently, rats were challenged, and anaphylactic reaction parameters including variations in plasma histamine levels, vascular permeability, systemic anaphylaxis scores, and total serum Immunoglobulin E levels were measured. After daily-gavaging for four weeks, quercetin completely abrogated peanut-induced anaphylactic reactions following challenges, so that the mean of plasma histamine levels in the quercetin-treated rats, were lower significantly (p=0.004) as compared with positive control group. Our findings suggest that the flavonoid quercetin is potent enough to suppress the on-going Immunoglobulin E responses against peanut proteins, and can be propounded as an alternative medicine to protect against Immunoglobulin E-mediated food allergies.

The effects of electrical vagus nerve stimulation on plasma levels of histamine and serotonin in intact and sensitized guinea pigs

The effects of electrical vagus nerve stimulation on plasma levels of histamine and serotonin in intact and sensitized guinea pigs

Characterization of histamine release induced by fluoroquinolone antibacterial agents in-vivo and in-vitro.

Characterization of histamine release induced by fluoroquinolone antibacterial agents, levofloxacin and ciprofloxacin, was investigated in-vivo and in-vitro. Intravenous injection of levofloxacin and ciprofloxacin at 1-10 mg kg(-1) produced dose-related elevations in plasma histamine level in anaesthetized dogs. In contrast, levofloxacin was devoid of plasma histamine increment in anaesthetized rats at 100 mg kg(-1), whereas ciprofloxacin at the same dose caused endogenous histamine release. Levofloxacin and ciprofloxacin induced non-cytotoxic secretion of histamine from all mast cells tested in a concentration-dependent manner, whereas rat skin and peritoneal mast cells were thirty- to one-hundred-times less sensitive to the effect of fluoroquinolones as compared with the canine skin mast cells. These results suggest that the functional heterogeneity of mast cells from different species in histamine releasing activity of fluoroquinolones may exist, and that mast cells from the dog appear to be particularly sensitive to the effect of the fluoroquinolones.

Plasma histamine levels (H) during adjunctive H1-receptor antagonist treatment with loratadine in patients with active Inflammatory Bowel disease (IBD)

Histamine exerts a broad range of both proinflammatory and immunoregulatory effects in the body. Although there are somewhat controversial findings about the role of mast cells in Inflammatory Bowel Disease (IBD), recent immunologic findings suggest that mast cells, histamine and other immunomediators associated with a TH2-cell response may play a role in ulcerative colitis and in early lesions of Crohn’s disease, both chronic inflammatory disorders of the large bowel [1, 2], leading to bloody diarrhoea, anaemia, abdominal pain and weight loss. Tissue histamine content and mast cell secretion have been reported to be increased in affected mucosa and active flares of IBD [2–4], while urinary methylhistamine excretion was found to be low during remission [5]. Therefore, we performed an adjunctive antihistamine trial in IBD and explored plasma histamine levels during standard treatment with or without loratadine.

Lipoic acid suppresses compound 48/80-induced anaphylaxis-like reaction

Alpha-lipoic acid (LA), a naturally occurring dithiol compound, is an essential cofactor in metabolic reactions involved in energy utilization. LA improves glycemic control, reduces diabetic polyneuropathies, atherosclerosis, and allergic inflammation. The effects of LA on mast cell-mediated anaphylactic reactions, however, are unknown. LA dose-dependently inhibited systemic and passive cutaneous anaphylaxis-like reactions in mice induced by compound 48/80, a condensation product of N-methyl-p-methoxyphenethylamine and formaldehyde. Pretreatment with LA, prior to induction of the systemic anaphylaxis-like reaction with compound 48/80, reduced plasma histamine levels in a dose-dependent manner. In our in vitro study, LA decreased histamine release from rat peritoneal mast cells (RPMCs) triggered by compound 48/80. Moreover, an increase in calcium uptake activated by compound 48/80 was inhibited by LA. LA also significantly elevated intracellular cyclic adenosine-3',5' monophosphate (cAMP) levels in RPMCs. This inhibition of mediator release from RPMCs may be due to inhibition of calcium uptake and augmentation of intracellular cAMP levels. Based on these results, we suggest that LA may be a potential remedy for allergy-related diseases.

Neurohumoral mechanisms of the rat heart adaptation to overload

The present study confirms involvement of the sympathicoadrenal system in adaptation of heart to overload. Besides, at formation of chronic heart failure (CHF) there have been revealed a rise of the histamine and serotonin levels in blood plasma and myocardium as well as glucocorticoid hyperactivation.

Histamine H3 Receptor-Mediated Signaling Protects Mice from Cerebral Malaria

BackgroundHistamine is a biogenic amine that has been shown to contribute to several pathological conditions, such as allergic conditions, experimental encephalomyelitis, and malaria. In humans, as well as in murine models of malaria, increased plasma levels of histamine are associated with severity of infection. We reported recently that histamine plays a critical role in the pathogenesis of experimental cerebral malaria (CM) in mice infected with Plasmodium berghei ANKA. Histamine exerts its biological effects through four different receptors designated H1R, H2R, H3R, and H4R.Principal FindingsIn the present work, we explored the role of histamine signaling via the histamine H3 receptor (H3R) in the pathogenesis of murine CM. We observed that the lack of H3R expression (H3R−/− mice) accelerates the onset of CM and this was correlated with enhanced brain pathology and earlier and more pronounced loss of blood brain barrier integrity than in wild type mice. Additionally tele-methylhistamine, the major histamine metabolite in the brain, that was initially present at a higher level in the brain of H3R−/− mice was depleted more quickly post-infection in H3R−/− mice as compared to wild-type counterparts.ConclusionsOur data suggest that histamine regulation through the H3R in the brain suppresses the development of CM. Thus modulating histamine signaling in the central nervous system, in combination with standard therapies, may represent a novel strategy to reduce the risk of progression to cerebral malaria.

Effects of succinylated gelatin and 6%HES130/0.4 hemodilution on serum electrolytes and plasma histamine

Objective To investigate the effects of acute hypervolemic hemodilution(AHH)using 4% succomuylated gelatin and hvdmxvethvl starch on serum electrolyte and plasma histamine.Methods Sixty patients suffered from esophageal carcino-ma or colon carcinoma were randomized into 2 groups(n=30)receiving intravenously 15 ml/kg of succinylated gelatm(group G)or 6% HES 130/0.4(group H).AHH was conducted 10 min after anesthesia induction-Levels of Hot,serum electrolyte and plasma histamine were measured before AHH,5 min(T1),30 min(T2)of AHH,30 min(T3),1h(T4)and 3 h after AHH termination,respectively,AHH(T3).Results The levels of serum Na+,K+,Ca2+.Cl- and plasma histsmine at T1,T2,T3 and T4 were significantly lower and higher respectively than those at To,with no statistical difference between two groups at each same time-point.Conclusion AHH using succinylated gelatin or hydroxyethyl starch is safe although bringing slight change in serum electrolytes and plasma histamine levels. Key words: succinylated gelatin; Hydroxyethyl starch 130/0.4; Acute hypervolemic hemodilution; Histamine

Anti-Allergic Effects of Herbal Product fromAllium cepa(Bulb)

Allium cepa (Family Liliaceae) is a reputed Indian medicinal herb that is prescribed as an effective remedy for several ailments in the Ayurvedic system of medicine. The aim of this study was to evaluate its efficacy against various events responsible for Type I allergic reactions. A herbal fraction (ALC-02) from A. cepa (bulb) inhibited histamine release and attenuated intracellular calcium levels in Compound 48/80-induced rat peritoneal mast cells. It also prevented Compound 48/80-mediated systemic anaphylaxis while lowering histamine levels in plasma. ALC-02 suppressed carrageenan-induced rat paw edema. It inhibited eosinophil peroxidase activity and protein content in bronchoalveolar lavage fluid (BALF) of ovalbumin-challenged mice. In this experiment ALC-02 also caused a substantial reduction in lipid peroxidation in BALF/lung tissue and augmented superoxide dismutase activity in lung tissue. ALC-02 suppressed erythrocytic lysis caused by Triton X-100. A significant quenching of 1,1-diphenyl-2-picrylhydrazyl radical by ALC-02 was observed. The results have shown a promising anti-allergic profile of ALC-02 that could be attributed to its potential antihistaminic, anti-inflammatory, and antioxidant activities.

Multiple H1‐antihistamine‐induced urticaria

H(1)-antihistamines are widely used in the treatment of various allergic diseases. Particularly, a cornerstone of the management of chronic idiopathic urticaria is treatment with H(1)-antihistamines. However, a few cases of H(1)-antihistamine-induced urticaria have been reported. A 34-year-old woman presented with a 4-month history of recurrent urticaria, which was prominently exacerbated by the administration of H(1)-antihistamines. The patient consented to a provocation test of fexofenadine among drugs including cetirizine and hydroxyzine, which were suspected of inducing severe symptoms in episodes. One hour after challenge with 12 mg fexofenadine (one-fifth of the therapeutic dose), a urticarial reaction rapidly developed on nearly the entire body with remarkably increased levels of plasma histamine (190 nmol/L) and plasma leukotriene B4 (150 pg/mL). In challenge tests with other antihistamines, generalized urticaria occurred 5 and 1 h after intake of 10 mg loratadine and 10 mg bepotastine, respectively, whereas challenges with chlorpheniramine, mequitazine and azelastine were all negative. Skin prick tests with H(1)-antihistamines used in the challenges were all negative, indicating that the urticarial reactions after challenges with the causative drugs might not be immunoglobulin E-mediated. Among the causative drugs in our case, cetirizine and hydroxyzine are the piperazine derivatives, whereas fexofenadine, bepotastine, ebastine and loratadine are the piperidine derivatives. The chemical structures of both derivatives are very similar. Therefore, in this case, H(1)-antihistamine-induced urticaria may have been due to cross-reactivity between metabolites of these drugs, but not to drugs before metabolization. Hypersensitivity to H(1)-antihistamines should be considered when urticarial lesions worsen after H(1)-antihistamine treatment.

IL-4/IL-13 antagonist DNA vaccination successfully suppresses Th2 type chronic dermatitis

Atopic dermatitis (AD) is a chronic disease with a Th2-type-cytokine dominant profile. Several cytokines and related peptides have been used for the treatment of AD but they were ineffective because of their limited biological half-life. We have recently developed a highly efficient mouse dominant negative interleukin (IL)-4/IL-13 antagonist (IL-4DM), which blocks both IL-4 and IL-13 signal transductions. To examine the effects of IL-4DM in vivo in an AD model induced by the repeated exhibition of oxazolone (OX). Plasmid DNA was injected intraperitoneally to cause an experimental AD-like dermatitis. The effect was evaluated by ear thickness, histological findings, and mast cells counts in the inflamed skin. The plasma IgE and histamine levels were measured. Cytokine production in skin and splenocytes were also analysed. Mice treated with control plasmid developed marked dermatitis with mast cells and eosinophil infiltration, and had increased plasma IgE and histamine levels with a Th2 type splenocyte cytokine profile. Treatment with mouse IL-4 DNA augmented the ear swelling and thickness with an increased dermal eosinophil count, plasma histamine level, and production of splenocyte IL-4. However, IL-4DM treatment successfully controlled the dermatitis, decreased the mast cell and eosinophil count, and suppressed plasma IgE and histamine levels. Splenocytes produced an increased level of IFN-gamma. These data showed that the simultaneous suppression of IL-4/IL-13 signals successfully controlled Th2-type chronic dermatitis. IL-4DM DNA treatment is a potent therapy for AD and related diseases.

Involvement of the organic cation transporters in histamine uptake into human vascular endothelial cells

Increased plasma histamine levels lead to pathological events. Endothelial cells actively participate in histamine clearance by promoting its rapid uptake [1, 2, 3] via yet unidentified carrier(s), thus limiting the spread of the histamine signal. Since histamine is a substrate for organic cationic transporters (OCT2 andOCT3) [4], andOCT3 is expressed in human blood vessels [5], the objectivewas to test whether OCT2 and/or OCT3 is/are involved in the clearance of histamine by human umbilical vein endothelial cells (HUVEC).

Influence of two different stressors, weaning and immunization, on the plasma histamine level of organic farming piglets

Influence of two different stressors, weaning and immunization, on the plasma histamine level of organic farming piglets

Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-γ–producing CD8 + T cells

Food allergy is a serious and sometimes fatal condition for which there is no cure. We previously reported that Food Allergy Herbal Formula (FAHF)-2) protected peanut-allergic mice against anaphylactic reactions as long as 4 weeks posttherapy. This formula is now in clinical trials in the United States. We sought to determine whether FAHF-2-mediated protection could be extended long-term and explored the mechanisms underlying its persistent immunomodulatory effects. Peanut-allergic mice received FAHF-2 daily orally by gavage for 7 weeks, and then received 7 oral peanut challenges at intervals of 4 to 10 weeks over a period of 36 weeks. For mechanistic studies, some mice received CD4(+) or CD8(+) T-cell-depleting antibodies or IFN-gamma-neutralizing antibodies. Anaphylactic symptoms, body temperatures, and plasma histamine levels were recorded after each challenge, and peanut-specific immunoglobulin levels and cytokine profiles of splenocytes, mesenteric lymph node cells, and purified CD4(+) and CD8(+) T cells were determined. Food Allergy Herbal Formula-2 treatment protected mice from anaphylaxis for more than 36 weeks after discontinuing treatment. Peanut-specific IgE levels were reduced as much as 50%, whereas IgG(2a) levels were increased as much as 60%, and these effects persisted over time. T(H)2 cytokine production by CD4(+) T cells from FAHF-2-treated mice was reduced as much as 75%, whereas CD8(+) T-cell IFN-gamma production was markedly increased by as much as 85% at the final challenge. Neutralization of INF-gamma and depletion of CD8(+) T cells markedly attenuated FAHF-2 efficacy. Food Allergy Herbal Formula-2 provides long-term protection from anaphylaxis by inducing a beneficial shift in allergen-specific immune responses mediated largely by elevated CD8(+) T-cell IFN-gamma production.

Modulation of Antigen-Induced Anaphylaxis in Mice by a Traditional Chinese Medicine Formula, Guo Min Kang

A traditional Chinese Medicine (TCM) formula, Guo Min Kang (GMK), has been used in clinics in China for allergic diseases, including type I immediate hypersensitivity, a potentially fatal disease, but its modulatory mechanism remains elusive. The aim of this study was to investigate the modulatory mechanisms of GMK in a mouse model of Ag-induced anaphylaxis. Ag (conalbumin) sensitized mice were treated with either PBS (sham) or GMK before (schedule A) or during (schedule B) sensitization, and various anaphylactic parameters were measured following Ag challenge, including symptom score, cutaneous hypersensitivity response, mast cell degranulation, plasma histamine levels and the levels of specific IgE and T-cell responses. Systemic anaphylaxis was investigated in mice immediately following Ag challenge, and the results showed that GMK-treated mice from both treatment schedules A and B showed significantly reduced symptom scores when compared with the sham-treated group. The reduction in symptom score was associated with a significant reduction in the level of Ag-induced cutaneous immediate hypersensitivity. Also, GMK was able to suppress Ag-induced IgE production and T-cell responses, while it spares mitogen (Con A)-induced T-cell response. Further, treatment of mice with GMK abrogated the levels of Ag-induced histamine release and significantly reduced the number of degranulated mast cells. No effect of GMK was observed on the levels of total IgE and plasma histamine in naive mice. These results provide a basis for the modulation effect of GMK and suggest a potential utility of GMK as a prophylactic and therapeutic agent.

Exogenous Histamine Aggravates Eczema in a Subgroup of Patients with Atopic Dermatitis

Food and beverages may contain high amounts of histamine and thus may cause symptoms after ingestion. The aim of this study was to investigate the role of ingested histamine in atopic dermatitis. Patients with atopic dermatitis had to maintain a histamine-free diet for one week. Consecutively, double-blind, placebo-controlled provocations were performed with histamine-hydrochloride and placebo. The clinical outcome was assessed by determination of the SCORAD. Before and 30 min after each provocation blood was collected for measurement of plasma histamine levels and diamine oxidase activity. Thirty-six patients with atopic dermatitis completed the diet. Twelve of 36 showed a significant improvement of the SCORAD after one week of the diet. After provocation tests 11 of 36 showed aggravation of eczema. Plasma histamine was significantly higher in patients with atopic dermatitis compared with controls (p><0.001), whereas diamine oxidase activity was similar in both groups. Our data indicate that ingestion of moderate or high amounts of histamine-hydrochloride may aggravate eczema in a subgroup of patients with atopic dermatitis. Plasma histamine and diamine oxidase activity were not associated with the clinical response to histamine.

Therapeutic effects of a fermented soy product on peanut hypersensitivity is associated with modulation of T‐helper type 1 and T‐helper type 2 responses

ImmuBalance is a koji fungus (Aspergillus oryzae) and lactic acid fermented soybean product. This unique production process is believed to create a food supplement that helps to induce or maintain normal immune response. To assess possible therapeutic effects of ImmuBalance on peanut (PN) hypersensitivity using a murine model of peanut allergy (PNA). PN allergic C3H/HeJ mice were fed standard mouse chow containing 0.5% or 1.0% ImmuBalance (ImmuBalance 2X), radiation-inactivated 1.0% ImmuBalance (I-ImmuBalance 2X), or regular diet chow (sham) for 4 weeks, beginning 10 weeks after the initial PN sensitization, and then challenged with PN. Anaphylactic symptom scores, plasma histamine, serum PN specific-IgE levels and splenocyte cytokine profiles were determined. While 100% of sham-treated PNA mice developed anaphylactic reactions with a median score of 3.3 following PN challenge, only 50% of ImmuBalance, 30% of ImmuBalance 2X and 40% of I-ImmuBalance 2X-treated mice developed allergic reactions with median scores of 1.0, 0.4 and 0.5 respectively, which were significantly less than that in the sham-treated mice (P<0.05). Plasma histamine and PN specific-IgE levels were also significantly less in all treated mice than in sham-treated mice (P<0.05). Furthermore, IL-4, IL-5 and IL-13 production by PN-stimulated splenocytes in vitro from ImmuBalance fed mice were markedly reduced compared with sham-treated mice, whereas IFN-gamma production was moderately increased. TGF-beta and TNF-alpha production were similar. ImmuBalance protects against PN-induced anaphylaxis when administered as a food supplement in this model. Protection was associated with down-regulation of Th2 responses. This supplement may provide a potential novel therapy for PNA.

VAMP-8 segregates mast cell–preformed mediator exocytosis from cytokine trafficking pathways

AbstractInflammatory responses by mast cells are characterized by massive exocytosis of prestored granular mediators followed by cytokine/chemokine release. The vesicular trafficking mechanisms involved remain poorly understood. Vesicular-associated membrane protein-8 (VAMP-8), a member of the soluble N-ethylmaleimide–sensitive factor (NSF) attachment protein receptor (SNARE) family of fusion proteins initially characterized in endosomal and endosomal-lysosomal fusion, may also function in regulated exocytosis. Here we show that in bone marrow–derived mast cells (BMMCs) VAMP-8 partially colocalized with secretory granules and redistributed upon stimulation. This was associated with increased SNARE complex formation with the target t-SNAREs, SNAP-23 and syntaxin-4. VAMP-8–deficient BMMCs exhibited a markedly reduced degranulation response after IgE+ antigen-, thapsigargin-, or ionomycin-induced stimulation. VAMP-8–deficient mice also showed reduced plasma histamine levels in passive systemic anaphylaxis experiments, while cytokine/chemokine release was not affected. Unprocessed TNF accumulated at the plasma membrane where it colocalized with a VAMP-3–positive vesicular compartment but not with VAMP-8. The findings demonstrate that VAMP-8 segregates secretory lysosomal granule exocytosis in mast cells from cytokine/chemokine molecular trafficking pathways.

Phlomis umbrosa root inhibits mast cell‐dependent allergic reactions and inflammatory cytokine secretion

The effect of an aqueous extract of Phlomis umbrosa Turcz. (Labiatae) root (PUAE) on mast cell-dependent allergic reactions and inflammatory cytokine secretion were investigated. PUAE (0.01-1 g/kg) inhibited compound 48/80-induced systemic allergic reaction. When PUAE was employed in a systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. PUAE (0.1 and 1 g/kg) also significantly inhibited the local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. PUAE (0.001-1 mg/mL) dose-dependently inhibited the histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. PUAE (0.01-1 mg/mL) inhibited the secretion of interleukin (IL)-1beta in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells. PUAE (1 mg/mL) inhibited the gene expression and production of the main inflammatory cytokine, TNF-alpha, in HMC-1 cells. These results provide evidence that PUAE may be beneficial in the treatment of allergic diseases.