Blood Histamine Levels Research Articles

Cutaneous response to intradermal histamine in lung cancer

Recent evidence has suggested that human neoplastic patients show decreased blood histamine levels and cutaneous responses to intradermal histamine. In this study we evaluate the skin response to intradermal injections of histamine and IgE levels in 34 male patients with lung cancer (of which 21 had metastasis) and in 16 control subjects. Analysis of our data does not reveal any difference in the areas of wheal and flare between control subjects and lung cancer patients with or without metastasis. Moreover the evaluation of the different histologic cell type of lung cancer provides the same results. In addition, the sensitivity (Histamine Threshold Concentration) and reactivity (slopes) to histamine is not statistically different. No difference is found for IgE levels between controls and cancer patients. In the light of our finding we believe that in lung cancer patients skin response to intradermal histamine is not decreased, and therefore that the hypothesis concerning the existence of H1-histamine receptor antagonist released by tumour is not confirmed.

Central action of somatostatin analog, SMS 201-995, to stimulate gastric acid secretion in rats

The effects of intracisternal and intravenous injections of the somatostatin analog, SMS 201-995, on gastric acid secretion were investigated in rats with pylorus ligation or gastric cannula. Intracisternal injection of SMS 201-995 induced a dose-related (0.1–0.3 μg) and long-lasting stimulation of gastric acid output with a peak response at 3 h postinjection in conscious, pylorus-ligated rats. Intracisternal SMS 201-995 increased histamine levels in the portal blood, whereas plasma gastrin levels were not modified. Atropine, cimetidine and adrenalectomy abolished the stimulatory effect of intracisternal SMS 201-995 (0.3 μg). SMS 201-995 (0.03 μg), microinjected unilaterally into the dorsal vagal complex, increased gastric acid output in urethane anesthetized rats. SMS 201-995, injected intravenously at 0.5 μg, did not alter gastric secretion, whereas higher doses (5–20 μg) resulted in a dose-related inhibition of gastric acid secretion in conscious pylorus-ligated rats. These data indicate that SMS 201-995, a selective ligand for somatostatin-1 receptor subtype, induces a centrally mediated stimulatory effect on gastric acid secretion in rats. The central action involves the parasympathetic system, muscarinic and H 2 receptors as well as adrenal-dependent pathways.

Blood histamine level in rabbits experimentally immunized with soluble elastin

Experimental immunization of rabbits with soluble porcine elastin was performed. An increase in histamine level in blood of immunized animals was observed.

Effect of Ascorbic Acid Nutriture on Blood Histamine and Neutrophil Chemotaxis in Guinea Pigs

Histamine suppresses certain immune responses, including neutrophil chemotaxis. The present study examined whether the histamine-lowering effect of ascorbate was accompanied by enhanced chemotaxis in guinea pigs. Animals were fed low ascorbate, adequate or high ascorbate diets (0.5, 2.0 or 50 mg ascorbate.100 g body wt-1.d-1) for 4 wk. Mean liver ascorbate paralleled dietary intake, and these values differed significantly. Blood histamine was significantly depressed in the high ascorbate group compared to the adequate and low ascorbate groups, and liver ascorbate was inversely correlated to blood histamine levels (r = -0.64, P less than 0.001). The random migration of neutrophils was not significantly affected by vitamin dosage. Leukocyte chemotaxis was significantly impaired in low ascorbate animals compared to that of animals with adequate ascorbate nutriture. Leukocyte chemotaxis in high ascorbate animals did not differ significantly from that in the adequate or low ascorbate groups. Furthermore, chemotaxis was significantly lower when cells extracted from animals with adequate ascorbate nutriture were incubated in low ascorbate or high ascorbate serum rather than in autologous serum. These data suggest that the histamine-lowering effect of supplemental ascorbate does not appear to enhance leukocyte chemotaxis and that serum from guinea pigs fed low or high levels of ascorbate appears to contain factors that depress chemotaxis.

A synergism of antigen challenge and severe magnesium deficiency on blood and urinary histamine levels in rats.

The effects of severe and moderate magnesium (Mg) deficiency on blood and urinary histamine were studied in 36 male weanling Sprague-Dawley rats with or without IgE-stimulating antigen challenge. The rats were divided into six groups: two each on 50 (severely deficient), 300 (moderately deficient), and 2000 (control) ppm Mg diets without and with immunization with ovalbumin challenge on days 0, 14, and 29. Unimmunized severely Mg-deficient rats had significantly elevated urinary histamine which returned to normal by 22 days, but whole blood histamine was still significantly elevated at 36 days. Both blood and urinary histamine of immunized severely Mg-deficient rats were significantly higher than those of all the other groups throughout the study, particularly after the antigen challenge. There was a synergism of antigen challenge and severe Mg deficiency on blood and urinary histamine levels. The results suggest that severe Mg deficiency can aggravate diseases which are caused by abnormal histamine release after exposure to an IgE-stimulating antigen.

Effects of coenzyme Q10 in hemorrhagic shock

We studied the effects of coenzyme Q10 (CoQ10) on pulmonary function and chemical mediators in a canine model of hemorrhagic shock. One group received 10 mg/kg of CoQ10 before hemorrhage. During the study, percent change from baseline of peak airway pressure, total lung compliance of the lung and chest wall, and blood lactate levels appeared to be significantly smaller in dogs pretreated with CoQ10 than in controls. Furthermore, CoQ10 was found to maintain blood histamine levels and to attenuate the increase in leukotriene C4. The mechanism of the beneficial effects of CoQ10 in hemorrhagic shock is presently unknown, but our data suggest that it may be useful in the treatment of hemorrhagic shock.

An experimental model of death from anaphylactic shock with compound [formula omitted] and postmortem changes in levels of histamine in blood

The present study was made on an experimental animal model of a death from anaphylaxis, in which postmortem changes in levels of histamine and 1-methylhistamine, in whole blood were measured. Instead of the usual immunological method administering compound 48 80 , a degranulating agent of mast cell and the effect closely resembling the immuno-reaction, resulted in reliable death in a short time. The animals that died rapidly after the injection of compound 48 80 , were found to have large increases in levels of histamine and 1-methylhistamine soon after the administration. These results were similar to the results of injecting histamine exogenously. On the other hand, the animals that died after a longer time showed no increases in levels of those amines within about 24 h, but 24 hours after death histamine levels were only increased tremendously without rise in 1-MHA levels. These phenomena closely resembled those in the control animals that were treated with overdoses of Nembutal ®.

The effects of intravenous endotoxin on various host-effector molecules

To understand better the pathogenesis of gram-negative infections, we administered a single intravenous injection of Escherichia coli RE-2 endotoxin (4 ng/kg) to five normal volunteers and periodically measured various host-effector molecules in blood. All subjects had a significant ( p < 0.05) increase in temperature (maximum of 1.3 ± 0.1 ° C at 4 hours) and white blood cell count (maximum of 7700 ± 1800 cells per cubic millimeters at 8 hours). Thymocyte costimulatory activity in blood was markedly increased 2 hours after endotoxin administration but returned to baseline at 4 hours. Blood cortisol and β-endorphin levels paralleled each other, peaking 4 hours after endotoxin (mean increases of 21 ± 14 (μg/dl and p < 0.01; 18.6 ± 5.9 pg/ml and p < 0.05, respectively) and returning to baseline at 8 hours. Blood histamine levels did not significantly change at any time point after endotoxin administration. Since thymocyte costimulatory activity was the first of the measured parameters to achieve peak blood levels, we suggest that endotoxin-induced increases in various cytokines may contribute to the increases in the other measured parameters and thereby play a significant role in the pathogenesis of gram-negative infections.

Blood Histamine Levels in HIV-1-Infected Infants and Children

Blood histamine levels (BHL; ng histamine base/ml blood, mean +/- SEM) were determined in 118 infants born to HIV-1-infected mothers and in children infected after blood transfusion. In asymptomatic infected infants, BHL were not significantly different from HIV-1-negative infants born to HIV-infected mothers (54.1 +/- 5.6 vs. 56.4 +/- 3.5). BHL progressively decreased in the group with polyadenopathies (40.0 +/- 4.0), in the group with AIDS-related complex (28.8 +/- 2.9), and in patients with AIDS (20.4 +/- 0.9). The decrease in BHL was associated with a decrease in blood basophil number.

Comparison between number of basophils, blood histamine, and histamine release in cancer and noncancer patients

In cancer patients with primary tumor with or without metastasis or metastasis alone, by comparison with healthy subjects and noncancer patients, the decrease in blood histamine levels is due to a decrease in total basophil number. These basophils have a normal content of histamine (1 to 2 pg per basophil) and are able to release histamine. The percentage of anti IgE-induced histamine release is not significantly different than in noncancer patients. The scarcity of basophils in cancer patients is not due to a leukopenia. Blood histamine levels and total basophil number are normal in patients after successful excision of their primary tumor without metastasis.

Alpha-fluoromethylhistidine in the treatment of idiopathic cold urticaria.

Alpha-fluoromethylhistidine (alpha-FMH), a new irreversible inhibitor of mammalian histidine decarboxylase, was tested in the treatment of idiopathic cold urticaria in 11 patients. In the initial trial with 50 mg b.i.d., a significant decrease (about 30%) in the total blood histamine level was found after 3 weeks of treatment but clinically there was no improvement in the symptoms of ten cold urticaria patients nor in the responses to the ice-cube test. In the second trial with three patients suffering from severe idiopathic cold urticaria, a higher dose of up to 500 mg b.i.d. of alpha-FMH for 3 weeks resulted in a marked decrease in the total blood histamine level as well as in an apparent inhibition of histamine synthesis in the skin previously exposed several times to cold water. The symptoms of cold urticaria and the responses in the ice-cube tests also decreased simultaneously. No clinical side effects nor changes in laboratory analysis were seen during the treatment with alpha-FMH. These results suggest that alpha-FMH may be useful in the treatment of severe cold urticaria especially in combination with histamine exhaustion of mast cells using cold water.

Use of plasma histamine levels to monitor cutaneous mast cell degranulation

A simple, minimally invasive procedure for monitoring cutaneous mast cell degranulation in vivo in man is described. Plasma histamine levels in venous blood draining the site of intradermal histamine, morphine, and antigen challenges were determined with a modified radioenzymatic assay. Elevations in plasma histamine above baseline levels of 0 to 0.6 ng/ml were measured after intradermal histamine; levels of 1.4 to 85.2 ng/ml were obtained after a 2 μg intradermal challenge in 16 subjects. After antigen testing, peak plasma histamine levels ranged from 1.1 to 24.4 ng/ml ( n = 9), and after morphine sulfate skin testing peak plasma histamine levels ranged from 2.3 to 12.7 ng/ml ( n = 4). The time to achieve peak plasma histamine levels ranged from 2 to 10 minutes after histamine, from 5 to 15 minutes after antigen, and from 1 to 8 minutes after morphine challenges. Plasma levels returned to baseline within 30 minutes after histamine and morphine challenges but took more than 60 minutes for antigen challenges. With careful choice of the skin test site in relation to venous drainage, plasma histamine increases after either histamine or antigen were reproducible and reliable. Plasma histamine levels peaked 5 to 10 minutes before maximal development of the wheal-and-flare responses after histamine, antigen, or morphine skin tests. The wheal-and-flare skin tests continued to increase in magnitude despite rapidly declining plasma histamine levels. Thus skin tests eliciting reactions ordinarily seen in an allergist's office cause measurable increases in plasma histamine levels that can be used to directly monitor mast cell degranulation in man in vivo. This procedure should prove useful in analyses of mast cell activation in vivo, particularly in the assessment of pharmacologic agents thought to influence mast cell reactivity.

Blood histamine concentrations are not elevated in humans with septic shock.

Histamine has been suggested as an important mediator of the cardiovascular abnormalities during septic shock. To determine if blood histamine levels were increased during human sepsis and septic shock, plasma histamine was measured using a very sensitive radioenzyme assay employing histamine N-methyltransferase (HNMT) in the following patient groups: normal controls (n = 76), nonseptic critically ill (n = 12), nonseptic shock (n = 2), sepsis without shock (n = 28), and septic shock (n = 41). Using this enzyme binding assay, all these groups had similar, normal plasma histamine concentrations, except those patients with septic shock whose mean histamine measurements were significantly reduced (p less than .002). This decrease was found to be due to an artifact of the assay: plasma contained a circulating inhibitor that falsely lowered the measured histamine level. Fractionation of septic shock plasma using molecular exclusion membranes and gel filtration revealed a 5000 MW inhibitory factor. After removal of this inhibitor from plasma, septic shock plasma histamine levels were normal. Thus, septic shock patients may have a circulating inhibitor of the HNMT enzyme, but plasma histamine concentrations are normal. Histaminemia is unlikely to play an important role in the pathogenesis of septic shock in humans.

Blood histamine and solid malignant tumors.

A clinical study was performed to determine whether patients with a newly diagnosed solid malignant tumor manifest an alteration in whole-blood histamine levels. Our results indicate that such patients have blood histamine nearly three times greater than either normal, healthy individuals or noncancerous disease controls. Following surgical removal of the tumor, blood histamine levels remained high for 2 months and then dropped close to the normal range 3 months after surgery. Basophil counts did not change significantly in the presence of a malignant tumor. Patients receiving either chemotherapy or radiation therapy, and terminal cancer patients who were no longer receiving any therapy except for pain control had blood histamine within or below the normal range. By analogy with animals studies, we suggest that nascent histamine synthesis is increased in the presence of a developing tumor. The clinical usefullness of this observation remains to be determined.

Plasma histamine profiles in paediatric cardiopulmonary bypass.

We have previously reported our findings of very high plasma histamine levels in the extracorporeal blood primes of infants undergoing cardiopulmonary bypass (CPB) for correction of congenital cardiac defects and have now extended this enquiry to examine the whole peri-operative period. In this preliminary study, samples of blood for plasma histamine were drawn from a mixed group of congenital cardiac patients featuring varying degrees of cyanosis, differing hypothermic operative conditions and utilising two oxygenator systems. Despite the diversity of this group a common pattern of histamine release emerged with a clear origin at the commencement of bypass, and continuing during the operative period. Our results suggest that priming procedures using stored donor blood provide a major contributing source of histamine release with inevitable deleterious consequences to the post-operative outcome.

Effect of pathological blood histamine levels on canine coronary vascular permeability.

We evaluated the effect of systemically administered histamine on coronary vascular permeability (CVP) of pentobarbital-anesthetized, open-chest dogs with and without beta-receptor blockade. We determined changes in CVP by comparing prenodal cardiac lymph flow and lymph-to-plasma protein concentration ratio before and after 30 min of histamine infusion. Histamine was infused into the left ventricle at 150 micrograms/min to produce pathological blood histamine concentrations of approximately 0.5 micrograms/ml. Histamine increased CVP in only one of seven dogs without beta-receptor blockade but increased CVP in four of seven beta-blocked animals. In a second series of experiments, the effect of histamine on CVP was assessed in an in situ isolated heart-lung preparation. In this preparation, similar blood histamine concentrations increased CVP in the same fraction of experiments (4 of 7) as was observed for beta-blocked dogs. Therefore, isolating the heart from the effects of all systemically derived histamine antagonistic substances did not appear to make the coronary vessels any more vulnerable to histamine than only blocking the actions of catecholamines. We conclude that 1) catecholamines provide protection for the coronary microvasculature against histamine-induced increases in the CVP; and 2) the probability that vascular permeability will increase in the heart when histamine exposure occurs through the general circulation is remote. Thus, if histamine-induced increases in CVP occur, then they probably result from the release of histamine from myocardial storage sites.

Circulating concentrations of histamine, neutrophil chemotactic activity, and catecholamines during the refractory period in exercise-induced asthma

Circulating mediators and catecholamine concentrations have been measured in eight subjects with asthma who were subjected to two bouts of cycle ergometer exercise separated by 1 hour. The maximum falls in FEV 1 were 21.9 ± 2.3% (mean ± SEM; n = 8) and 5.5 ± 1.3% (mean ± SEM; n = 8) after the first and second exercises, respectively. Serum neutrophil chemotactic activity (NCA) and plasma histamine and catecholamine levels in venous blood were measured with a microchemotaxis and two radioenzymatic techniques, respectively. There was a significant increase in NCA and plasma histamine concentrations after both exercise challenges, and there was no significant difference in the release of these mediators between the two exercise tests. Gel filtration chromatography demonstrated that the NCA detected after the first and second exercise tests had molecular sizes of approximately 600,000 daltons. There was no significant time-dependent increase in plasma norepinephrine and epinephrine concentrations after either exercise task, even though the patients were refractory to exercise-induced asthma after the second exercise. These results suggest that the refractory period in exercise-induced asthma is not caused by mediator depletion, as indicated by NCA and histamine measurements, or by protection of the airways through catecholamine release.

Mast Cell Participation During the Elicitation of Murine Allergic Contact Hypersensitivity

In order to evaluate mast cell participation in allergic contact hypersensitivity (ACH), BALB/c mice were sensitized with 0.1% trinitrochlorobenzene (TNCB). Immediately before challenge and at 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after challenge with 1% TNCB, groups of animals had ear thickness measured, had blood collected for histamine determinations, and had both ears removed for histologic evaluation of mast cells. The increase in ear swelling was triphasic with peak increases at 1.5 h (14.3 +/- 1.6 X 10(-2) mm; mean +/- SEM), 8 h (19.9 +/- 1.8 X 10(-2) mm), and 24 h (30.2 +/- 2.9 X 10(-2) mm). A triphasic pattern of increased serum histamine was noted at 1-4 h (117% over control levels), at 12 h (131%), and at 48 h (133%). Examination of the tissue specimens from challenged animals showed modest (1+) degranulation of mast cells between 1 and 6 h with extensive (2+) degranulation at 12 h. In addition, hypogranulated mast cells were evident between 1 and 6 h, at 24 h, and at 48 h. There were no statistically significant differences in mast cell numbers at any time. Neither platelets nor other formed elements of the blood contributed to the increased blood histamine levels. These data show that mast cells are activated in a triphasic pattern during ACH, and thus suggest both early and late roles for the mast cell and its products in the evolution of ACH.

Effect of microfiltration on the histamine levels in stored human blood.

Plasma and whole blood histamine levels and white cell counts have been monitored over a 6-week period of storage in standard citrate-phosphate-dextrose supplemented with adenine (CPDA) blood packs, add-back blood packs, and also CPDA and add-back packs which were subjected to a microfiltration process at the time of collection. Our results indicate that the plasma histamine level rises and the white blood count falls progressively with time, the former being most marked after the 3rd week of blood storage. At 6 weeks, there was no significant difference between the plasma and whole blood histamine level, suggesting that the entire complement of histamine in blood was now in plasma. Microfiltration substantially reduced the white cell count in the packs, and this was reflected in a greatly reduced whole blood and (subsequently) plasma histamine concentration.

Whole Blood and Plasma Histamine in Common Migraine

Whole blood and plasma histamine levels were measured in 27 non-medicated patients with common migraine. In nine cases blood was drawn 1-2 h after the onset of a migraine attack. The whole blood histamine levels of migraineurs and controls did not differ significantly. In contrast, histamine levels were significantly increased in plasma from patients both during and between migraine attacks, as compared with controls (p less than 0.001). Finally, plasma taken from migraine patients induced a significantly greater release of histamine from control whole blood than did plasma taken from control subjects (p less than 0.01).