Spontaneous Histamine Release Research Articles

A comparison of the inhibitory effect of cromoline and nedocromil Na on histamine release from airway metachromatic cells and from peripheral basophils

Metachromatic cells are increased in the airways of asthmatic patients. We obtained metachromatic cells from asthmatic airways using an induced sputum technique. The histamine release following ConA, anti-IgE and anti-IgE + IL 3 from those cells were evaluated before and following the addition of cromoline Na and nedocromil Na. Metachromatic cells had a higher rate of spontaneous histamine release when compared to peripheral basophils. Cromoline Na and nedocromil Na inhibited histamine release from triggered metachromatic cells but not from peripheral basophils. It is concluded that airway metachromatic cells from asthmatics behave differently than peripheral basophils.

Modulation of histamine release by sodium, potassium adenosine triphosphatase inhibition.

Previous studies have shown that a sodium, potassium adenosine triphosphatase inhibitor is present in the plasma of allergic subjects in whom enhanced histamine releasability has also been reported. The purpose of this study was to determine the effect of in vitro sodium, potassium adenosine triphosphatase inhibition on whole blood histamine release. Samples obtained from 12 patients with allergic rhinitis and 12 nonallergic subjects were incubated in duplicate for 30 minutes with anti-IgE antibody (100 micrograms/mL) or control buffer following a 0-, 10-, 20-, 30-, 60-, 120- and 180-minute preincubation with ouabain (3.0 mM) or diluent. Cell supernatants were assayed for histamine by radioimmunoassay and results were expressed as a percentage of total histamine release. Mean (+/- 1 SEM) anti-IgE induced release, in the presence and absence of ouabain, respectively, for allergic subjects was 27.5 +/- 5.5 and 21.0 +/- 4.5 (ten minutes, P < 0.05), 30.3 +/- 6.0 and 22.4 +/- 4.8 (20 minutes, P < .025), 28.9 +/- 5.2 and 23.5 +/- 4.1 (30 minutes), 33.8 +/- 7.1 and 26.7 +/- 5.4 (60 minutes, P < .05), 43.2 +/- 7.5 and 24.3 +/- 4.6 (120 minutes, P < .001), and 34.5 +/- 5.0 and 29.8 +/- 5.4% (180 minutes). Spontaneous histamine release in allergic subjects was also significantly increased by ouabain. Mean (+/- SEM) spontaneous release, in the presence and absence of ouabain, respectively, for allergic subjects was 2.0 +/- 0.5 and 0.9 +/- 0.2 (60 minutes, P < .025), 2.8 +/- 0.5 and 1.9 +/- 0.4 (120 minutes, P < .05), and 5.4 +/- 1.5 and 3.9 +/- 0.8% (180 minutes, P < .005). Ouabain did not significantly alter histamine release in non-allergic subjects. These data show that ouabain induced a significant increase in both spontaneous and induced histamine release in allergic subjects. In vivo, sodium, potassium adenosine triphosphatase inhibition may have an effect on histamine release in allergic subjects.

Canine leucocyte histamine release: response to antigen and to anti-IgE.

Histamine release from canine leucocyte-enriched peripheral blood preparations was measured in atopic, non-atopic and artificially sensitised dogs after immunological challenge with D. farinae antigen and anti-IgE. Total cell histamine and spontaneous histamine release was also measured. The total cell histamine content of equal leucocyte preparations was not statistically significant between the atopic and non-atopic groups. At all dilutions of antigen a higher amount of histamine was released from the leucocytes of atopic dogs than was seen in the non-atopic group. No histamine release in response to D. farinae was seen in the sensitised dogs although a statistically significant increase in serum D. farinae-specific IgE could be demonstrated after sensitisation (P < 0.03). Histamine release in response to anti-IgE was significantly greater in the atopic dogs than the non-atopic dogs (P < 0.004) and the sensitised dogs (P < 0.003). There was no statistically significant difference in total serum IgE between the groups. The authors conclude that the leucocytes of atopic dogs have a greater tendency to release histamine than those of normal and artificially sensitised dogs and that this is independent of the concentration of total serum IgE or antigen-specific IgE. They suggest that there may be immunoregulatory abnormalities in atopic dogs intrinsic to the atopic state as is described in man.

Ex vivo pharmacologic modulation of basophil histamine release in asthmatic patients.

Histamine is one of a range of mediators which play an important role in asthma, and the "releasability" of basophils has been shown to be upregulated in this disease. In vitro, beta 2-agonists and to a lesser extent corticosteroids have been shown to reduce histamine release. The ex vivo effects of salmeterol and inhaled corticosteroids on histamine release were studied in 78 asthmatic patients with variable disease severity and 20 control subjects. Spontaneous and anti-IgE-induced histamine release was measured in all subjects. Fifteen patients were not receiving any form of treatment, 42 were treated with inhaled corticosteroids, and 21 received inhaled corticosteroids and salmeterol. Seven patients treated with inhaled corticosteroids and seven patients treated with inhaled corticosteroids and salmeterol were tested twice to assess the effect of salmeterol on histamine release. Nine patients treated with inhaled corticosteroids were tested before and after 1 month of salmeterol treatment to determine the possible inhibition by salmeterol. Patients who were treated with inhaled corticosteroids and salmeterol showed significantly lower levels of spontaneous histamine release (median: 2.5%) than untreated (5.2%) and inhaled corticosteroids-treated asthmatics (3.4%). No tachyphylaxis to salmeterol was observed when patients were tested twice at a 3-month interval. This study suggests that salmeterol may have an additive anti-inflammatory effect with inhaled corticosteroids, although this hypothesis must be tested by further studies involving cells obtained by bronchoalveolar lavage and studies with bronchial biopsies.

Histamine releasing cells of the newborn. Mast cells from the umbilical cord matrix and basophils from cord blood.

The cellular branch of the immune defence in the newborn has been shown to differ from adults in a number of ways. This report presents new data on the functions of the histamine-secreting cells of the newborn. Mast cells of the newborn were obtained from the human umbilical cord by enzymatic dispersion. The granules of the mast cells of the umbilical cord were found to contain both chymase and tryptase by immunohistochemical staining, and the presence of cell-bound IgE on the mast cell surface was demonstrated by staining sections of umbilical cord with peroxidase-conjugated anti-IgE. The enzymatic dispersion yielded 12,660 mast cells per gram umbilical cord (median), range 2,500-60,300 (n = 48). The mast cells were found to constitute 3.1% of the total nucleated cells in the dispersate (median), range 1.5-3.8%. The histamine release from these cells was measured using a glass microfibre-based method. Both the umbilical cord mast cells and the cord blood basophils released histamine stimulated with anti-IgE, concanavalin A and the calcium ionophore A23187. In contrast to mast cells from adult tissue, the phorbol ester TPA was found to be an efficient secretagogue in both mast cells and basophils from the newborn. After maximal stimulation with anti-IgE and phorbol ester the quantity of histamine released per millilitre of blood was significantly higher in cord blood than in adult blood. The spontaneous histamine release from cord blood basophils was also significantly higher than from adult blood basophils. The mast cells found in the umbilical cord matrix and the cord blood basophils represent a readily available source of metabolically active histamine releasing cells for exploration of the role of histamine-secreting cells in newborn immune defence.

Time-dependent histamine release from stored human blood products

Perioperative transfusion of whole blood has been shown to amplify trauma-induced immunosuppression, which could be attenuated by perioperative administration of histamine2 receptor antagonists. Supernatants from different blood products were, therefore, analysed for histamine content during storage. Whole blood (six units), plasma-reduced whole blood (six units), and plasma- and buffy coat-reduced (saline-adenine-glucose-mannitol) (SAGM) blood (six units) from unpaid healthy donors were stored in the blood bank for 35 days at 4 degrees C. Plasma histamine and total cell-bound histamine content at donation, and histamine concentration in samples drawn from the units on days 0, 2, 5, 9, 14, 21, 28 and 35 were analysed with an enzyme-linked immunosorbent assay. Median plasma histamine concentration was 4.8 (range 1.9-14.3) nmol/l (n = 18). Median total cell-bound histamine content was 417.0 (range 176.0-910.0) nmol/l in whole blood and 475.0 (range 360.0-1560.0) nmol/l in plasma-reduced whole blood, while it was undetectable in SAGM blood. Spontaneous histamine release increased in a time-dependent manner from a median of 6.7 (range 2.2-17.4) nmol/l at the time of storage to 175.0 (range 33.0-485.0) nmol/l at day 35 in whole blood, from 18.8 (range 8.2-38.5) to 328.5 (range 224.0-1137.0) nmol/l in plasma-reduced whole blood, and from 0.5 (range 0.5-1.5) to 2.2 (range 1.4-6.9) nmol/l in SAGM blood. These results show spontaneous histamine release during storage of human blood products which contain full amount of leucocytes, and this may play a significant role in detrimental effects of blood transfusion.

Effect of interleukin-1 receptor antagonist (IL-1RA) on histamine and serotonin release by rat basophilic leukemia cells (RBL-2H3) and peritoneal mast cells.

Recently, it has been appreciated that cultured mast cells are significant sources of cytokines. However, the role of interkeukin-1 (IL-1) on mast cells and/or basophil degranulation is still unclear. In this report we provide evidence that rat basophilic leukemia cells (RBLC) cultured with a natural inhibitor of IL-1, interleukin-1 receptor antagonist (IL-1RA) (500 ng/ml) for 48 h, strongly inhibited the spontaneous release of serotonin (5HT) and histamine (from 22.50 to 43.49%), compared to untreated cells (control). When IL-1RA-treated and untreated RBLC were stimulated with a secretagogue (anti-IgE), no difference was found in the percent of 5HT and histamine release. Moreover, in another set of experiments using rat peritoneal mast cells (RPMC) treated and untreated with IL-1RA, we found that IL-1RA did not affect the release of 5HT or histamine, even when the secretagogue anti-IgE or compound 48/80 (C48/80) were used. The present studies describe an additional biological activity of IL-1RA, inhibiting histamine and 5HT release from RBLC cultures.

Modulation of histamine release from mast cells by interleukin-2 is affected by nedocromil sodium

We have previously demonstrated that histamine release from immunologically activated mast cells (MC) is enhanced by their preincubation (1 h) with interleukin-2 (IL-2), and that IL-2 induces slow-chronic histamine release by MC in long-term cultures (6 days). In the present study we assessed whether nedocromil sodium can interfere with IL-2 modulation of MC histamine release. IL-2 enhancing effects and nedocromil sodium activity were studied in cocultures of rat peritoneal MC with 3T3 fibroblasts (MC/3T3). MC/3T3 were preincubated for 1 h with IL-2 (50 μg/ml) and activated with either rabbit anti-rat IgE or compound 48/80. In chronic experiments MC/3T3 were long-term (5–6 days) incubated with IL-2 (50 pg/ml). Nedocromil sodium was used at 10 −5 M. Nedocromil sodium markedly inhibited the enhancing effect of IL-2 on compound 48/80 and anti-IgE mediated MC activation both when added during the preincubation period (no tachyphylaxis was present) and when added together with the MC activators (30–50% inhibition). Washing out IL-2 before addition of the anti-IgE antibodies did not affect its histamine-release enhancing activity. Removal of nedocromil sodium before addition of the stimulus completely abrogated its effect. Continuous presence of IL-2 in the culture medium enhanced spontaneous histamine release by 37% and this effect was completely abolished in the presence of nedocromil sodium. Furthermore, nedocromil sodium decreased MC basal histamine release by 23% in long-term cocultures. Since IL-2 is known to be elevated in some pathological conditions, our results show that nedocromil sodium inhibits MC activation in an in vitro system which may represent a close resemblance to the in vivo allergic response.

The Effects of Tumour Necrosis Factor α on Mediator Release from Human Lung

Summary: Although tamour necrosis factor α (TNFα) may be involved in the pathology of asthma, little is known about its role in mediator release from inflammatory cells in human lung. We investigated whether TNFα induced histamine release from mast cells in human chopped lung tissue and whether it modulated antigen-induced release of histamine and leukotrienes C 4/D 4/E 4 from passively sensitized lung tissue. Spontaneous histamine release in the presence of 1 nM TNFα for up to 4 h at 37°C was not significantly different from spontaneous histamine release alone (6.1±1.3% and 6.1±1.5% of total tissue histamine at 4 h respectively; n=3). Lung tissue was passively sensitized to the house dust mite Dermatophagoides pteronyssinus by incubating it in serum from an atopic volunteer donor for 3 h at 37°C. Treatment of the sensitized lung tissue with 1 nM TNFα for 60 min prior to challenge with a low concentration (1.8 AU) of D. pteronyssinus caused a significant increase in the amount of histamine release induced by the antigen from 0.2±0.6% to 1.9±1.0% of total tissue histamine ( P=0.045, n=6). The release of leukotriene C 4/D 4/E 4 induced by the same concentration of antigen was not significantly changed by the TNFα treatment (39.5±9.1 and 55.6±17.7 pg/100 μl supernatant sample respectively; n=6). These results suggest that TNFα may be involved in potentiation of histamine release in allergic asthma, particularly in the presence of low antigen concentrations.

Chemokines of the α, β-subclass inhibit human basophils' responsiveness to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1

Monocyte chemotactic and activating factor (MCAF) is the most potent cytokine that activates basophils to release histamine. The response of human basophils to either simultaneous or sequential addition of the chemokines RANTES, macrophage inflammatory protein (MIP)-1α, MIP-1β, platelet factor (PF)4, connective tissue activating peptide III (CTAP-III), interleukin (IL)-8, and inflammatory protein (IP)-10 on MCAF-induced histamine release was studied. Simultaneous addition of MCAF and any of the chemokines studied evoked an augmented response as measured by histamine release, whereas preincubation of leukocytes or purified basophils (80%) with these chemokines decreased MCAF-induced histamine release in a dose-dependent manner. Histamine release by anti-IgE remained unchanged. When tested at 5 × 10-9 mol/L, the decrease in histamine release by RANTES was 69.2% ± 3.5%, by MIP-1α 48.8% ± 3.1%, by MIP-1β 42.9% ± 3.1%, by PF4 56.5% ± 2.9%, by IL-8 41.2% ± 2.2, by CTAP III 27% ± 4.4%, and by IP-10 15.3% ± 2.6%. The peak inhibition of histamine release by the chemokines was reached within 10 minutes of preincubation with basophils and remained unchanged thereafter. Washing basophils after preincubation with chemokines abolished the inhibition, with the exception of desensitization by low concentrations of MCAF. With the exclusion of MCAF and RANTES, none of the chemokines (at the concentration range of 5 × 10-8 to 5 × 10-11) induced significant (>10% above spontaneous) histamine release from basophils. Preincubation of basophils with C5a (5 × 10-10 mol/L) did not affect histamine release, whereas preincubation with granulocyte-macrophage colony-stimulating factor (10 ng/ml) or IL-5 (10 ng/ml) enhanced MCAF-induced histamine release by 121.8% ± 10.1% and 108% ± 10.8%, respectively. We have therefore characterized RANTES, MIP-1α, MIP-1β, CTAP III, PF4, IL-8, and IP-10 as inhibitors of MCAF-induced histamine release. Although the results are consistent with receptor blockade, the α and β chemokines appear to interact with separate receptors linked to G proteins; thus, a mechanism of receptor class desensitization is proposed. Interaction of this group of cytokines at the site of allergic inflammation may modulate a function of basophils to initiate, augment, or inhibit histamine release. (J ALLERGY CLIN IMMUNOL 1995;95:574-86.)

Effect of a helium-neon laser on cutaneous inflammation.

A Helium-Neon (He-Ne) laser with a wavelength of 632.8 nm is known to have photobiological effects and is widely used for reducing the pain of herpes zoster and accelerating wound healing, however the cellular mechanism and effect of the He-Ne laser are poorly understood. The present study was designed to examine the influence of He-Ne laser irradiation on irritant and allergic contact dermatitis of the mouse ear and on histamine release from rat peritoneal mast cells. Irradiation was applied with a He-Ne laser (12.2 J/cm2) at 1 h, 10 min, 5 min and 0 min before, and 5 min, 6 hs and 24 hs after a challenge of an irritated contact dermatitis (ICD) or allergic contact dermatitis (ACD) was made on the right ears of ICR-mice. Twenty-four hours after the challenge, the swelling of the ear was measured with a dial thickness gauge, and the anti-inflammatory effect of He-Ne laser irradiation was expressed as an ear thickness ratio (ETR). Although the laser did not decelerate the ETR from ICD, the allergic response was decelerated. Irradiation at 5 min after the challenge of contact dermatitis increased the thickness ratio. Next, the influence of the He-Ne laser on histamine release from Wistar-rat peritoneal mast cells was observed. The spontaneous histamine release was inhibited by laser irradiation, while substance P and compound 48/80-induced histamine release were not inhibited. From these results, it can be suggested that He-Ne laser irradiation has an anti-inflammatory effect on cutaneous inflammation.

P2-106 - The involvement of spontaneous release of endogenous acetylcholine and histamine in basal acid secretion in the mouse isolated whole stomach

P2-106 - The involvement of spontaneous release of endogenous acetylcholine and histamine in basal acid secretion in the mouse isolated whole stomach

Effect of taxol and cremophor el on spontaneous and adriamycin-induced histamine release in rat peritoneal mast cells

Effect of taxol and cremophor el on spontaneous and adriamycin-induced histamine release in rat peritoneal mast cells

Basophils and eosinophils in allergic rhinitis

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The effect of exercise on basophil histamine release in patients with bronchial asthma.

There is increasing evidence for the role of basophils in allergic bronchial asthma. We studied the potential role of basophils in the pathogenesis of post-exercise-induced bronchoconstriction by measuring the histamine release from basophils both spontaneously and following ConA, FMLP, anti-IgE and TPA treatment. Two groups of patients with allergic asthma were studied: group I consisted of 8 patients with an exercise-induced fall in FEV1 of 20% or more, and group II had 7 patients with bronchial asthma who had less than a 5% fall in FEV1 following exercise. The mean spontaneous histamine release (SHR%) from basophils for group I was significantly larger than that of group II both before as well as at 5-10 and 60 min following exercise. The SHR% at baseline was 25 +/- 10 in group I (mean +/- SD) and 15 +/- 5 in group II (mean +/- SD). At 5-10 min following exercise it was 24 +/- 6 in group I and 11 +/- 2 in group II, while at 60 min following exercise it was 24 +/- 6 in group I and 17 +/- 2 in group II. There was no significant difference between the two groups in the effect of ConA, FMLP, anti-IgE or TPA treatment on basophil histamine release. The enhanced bronchoconstriction by exercise did not affect histamine release either spontaneously or following those 4 stimuli. It was concluded that, although patients with exercise-induced asthma have a greater degree of spontaneous histamine release, this is not affected by induced bronchoconstriction, a finding which does not support a role for basophils in exercise-induced asthma.

PATIENTS WITH SEVERE ATOPIC DERMATITIS HAVE ACTIVATED CIRCULATING BASOPHILS

Patients with food allergy and clinically more severe atopic dermatitis had increased spontaneous basophil release of histamine and LTC4. The increase in basophil releasability in response to deuterium oxide suggests that circulating basophils in the severe atopic dermatitis group are more activated.

Involvement of apamin-sensitive K+ channels in antigen-induced spasm of guinea-pig isolated trachea.

1. In order to examine whether K+ channels play a role in antigen-induced airway responses, the effect of K+ channel blockers on antigen-induced airway smooth muscle contraction and mediator release was examined in vitro in guinea-pigs actively sensitized with ovalbumin (OA). 2. Tracheal strips from sensitized animals were suspended in organ baths under a resting tension of 1 g and isometric tension was continuously measured. Cumulative concentration-response curves to OA (0.1-1000 ng ml-1) or histamine (10 nM-1 mM) were obtained in the presence and absence of K+ channel blockers. 3. OA (10, 100 or 1000 ng ml-1) was incubated with minced lung tissues from the same animals for 15 min in the presence and absence of K+ channel blockers, and released histamine and leukotriene C4 (LTC4) in the incubating medium were measured. 4. Apamin, a small conductance Ca(2+)-activated K+ channel (PK,Ca) blocker, (0.1, 0.3 and 1 microM) significantly inhibited OA-induced smooth muscle contraction, while charybdotoxin (ChTX, 10 nM), an intermediate and large conductance PK,Ca blocker, and iberiotoxin (IbTX, 3 nM), a large conductance PK,Ca blocker, were without effect. Apamin (0.3 microM) had no effect on exogenously administered histamine-induced airway smooth muscle contraction, suggesting that the inhibition of OA-induced contraction by apamin did not occur at the smooth muscle level. 5. The inhibition of OA-induced contraction by apamin (0.3 microM) was not significantly affected by pretreatment with a leukotriene antagonist, ONO-1078 (10 microM), but was abolished by pretreatment with a histamine H1-receptor blocker, pyrilamine (1 microM). 6. Apamin by itself (up to 0.1 MicroM) had no effect on spontaneous histamine release from minced lung tissues. Histamine release induced by low and intermediate concentrations of OA (10 and 100 ng ml-1)was significantly suppressed by apamin pretreatment (P<0.05 and P<0.001), whereas LTC4 release was not affected. ChTX (0.1 MicroM) and IbTX (10 nM) had no significant effect on either spontaneous or OA (100 ng ml-1)-induced histamine release.7. These results suggest that apamin partially but substantially inhibits antigen-induced smooth muscle contraction, presumably by inhibiting antigen-induced histamine release from airway mast cells through small conductance PKca closure.

Differential reactivity of human bronchoalveolar lavage mast cells to substance P.

Substance P (SP) stimulates human skin and rodent mast cells. Since neuropeptide-mediated reflexes may be important in asthma, the ability of SP to stimulate human mast cells obtained at bronchoalveolar lavage (BAL) was examined. Routine BAL (n = 22) samples were obtained and histamine release experiments performed in a standard manner. Spontaneous histamine release was bimodally distributed (Group A, high spontaneous release/Group B, normal spontaneous release). Further, Group A had significantly elevated corrected SP-induced histamine release compared to Group B but the corrected calcium ionophore A23187-induced responses were similar. No differences were found in clinical history, age, lavage return or total cell numbers between groups. However, differential cell counts revealed significantly elevated mast cell numbers in Group A providing further evidence for altered mast cell responsivity associated with mast cell hyperplasia. In asthma, BAL mast cells have increased spontaneous and stimulated secretory responses; thus, in asthma SP may also stimulate pulmonary mast cells.

IgE-receptor activated chloride uptake in relation to histamine secretion from rat mast cells.

1. Antigen-stimulated histamine secretion from rat peritoneal mast cells was inhibited when extracellular chloride was replaced by either isethionate or gluconate anions, but the histamine release still remained quite substantial. 2. Rat peritoneal mast cells take up 36Cl and the uptake reaches a steady state after 60 min incubation with the isotope. At steady state, the intracellular chloride level in the cells was calculated to be 29 +/- 11.5 mM. 3. The chloride uptake in mast cells was exponential with a rate constant of 0.036 min-1 in resting cells. When the cells were stimulated with antigen, and rate constant for chloride uptake increased to 0.90 min-1: an increase of 25 fold. Under identical experimental conditions histamine release increased 3 fold. 4. The rate of chloride uptake in either resting cells or in antigen-stimulated cells was not changed when the extracellular medium was nominally calcium-free but histamine release was almost completely inhibited in the absence of extracellular calcium. 5. The putative chloride channel blocker DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) 0.3 to 30 microM, produced a concentration-related inhibition of antigen-stimulated histamine secretion but DIDS (30 microM) did not inhibit the antigen-stimulated increase of chloride uptake. 6. The cyclic AMP analogue, dibutyryl cyclic AMP (1 mM) produced a delayed increase in chloride uptake in resting mast cells but neither dibutyryl cyclic AMP nor 8-bromo cyclic AMP per se induced any histamine secretion. 7. Ouabain (1 mM) which inhibits the Na+/K+ ATPase in rat peritoneal mast cells, failed to affect the uptake of chloride in resting mast cells. 8. The Na/K/2C1-cotransport inhibitor, furosemide (0.7 mM), slowed the unstimulated chloride uptake in resting mast cells and abolished the increased antigen-induced chloride uptake when added together with antigen. In contrast, spontaneous and antigen-induced histamine release were unaffected by the presence of furosemide. However, when furosemide was added to the cell suspension 5 min before stimulation, furosemide was without effect on the antigen-induced chloride uptake.9. In addition to the chloride uptake mediated by chloride channels which may be related to the mechanism of histamine secretion, crosslinking of the high affinity membrane receptors for IgE is followed by a fast chloride uptake that is likely to occur through a furosemide-sensitive Na/K/2C1-cotransporter.

Spontaneous histamine release in whole blood in patients before and after 4 months of specific immunotherapy.

Spontaneous histamine release (SHR) in whole blood was assessed before and after 4 months of specific immunotherapy (SIT) for allergic rhinoconjunctivitis in 32 patients. Spontaneous histamine release was significantly enhanced (P < 0.05) in patients prior to immunotherapy compared with 20 controls. Spontaneous histamine release decreased significantly in patients after 4 months of specific immunotherapy (P < 0.04) and almost reached the same values as spontaneous histamine release in controls. Clinical success of treatment after 4 months was seen in 15 patients (improvement > or =50%), 10 of whom showed a significant decrease in spontaneous histamine release. Decrease of spontaneous histamine release after 4 months indicates the efficacy of specific immunotherapy already at an early stage of treatment. Assessment of spontaneous histamine release appears to be a useful and easily performable method for monitoring success of treatment of patients during specific immunotherapy.