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PubMed1995

Effects of interleukin (IL)-13 on immediate-early response gene expression, phenotype and differentiation of human mast cells. Comparison with IL-4.

The recently cloned interleukin 13 (IL-13) shares most investigated biological activities on B lymphocytes and monocytes with IL-4. In this study we investigated the potential role of IL-13 in regulating human mast cell activities. The effects of IL-13 on the expression of an immediate-early response gene (c-fos), proliferation, expression of mast cell-associated cell surface antigen (CD54 and Kit), and in vitro differentiation of human mast cells, were investigated. We compared the effect of IL-13 with that of IL-4. Both IL-13 and IL-4 induced expression of c-fos in cells from the human mast cell line HMC-1. This indicates that mast cells express functional receptors for IL-13. IL-13 and IL-4 decreased the proliferation rate of HMC-1 cells. However, IL-13 was less potent than IL-4. Human mast cells constitutively express the adhesion molecule ICAM-1 (CD54) and the receptor for stem cell factor (Kit) (CD117). The expression of CD54 was increased after treatment with IL-13 or IL-4, whereas the expression of Kit was decreased. Also in this action IL-4 was more potent than IL-13. By culturing mononuclear cells from cord blood in the presence of stem cell factor there is a differentiation of tryptase-positive mast cells in the cultures. This process was inhibited when IL-4 was present. In contrast, IL-13 did not affect the expression of tryptase during differentiation of stem cell factor dependent cord blood-derived mast cells. Taken together, these findings indicate that IL-13 has regulatory effects on human mast cells. The effect overlaps with but is also different from that of IL-4.

Blotting, Northern↗
PubMed1997

Human mast cells express functional TrkA and are a source of nerve growth factor.

Mast cells are the principal effector cells in IgE-dependent hypersensitivity reactions. Despite reports that rodent mast cells proliferate in the presence of nerve growth factor (NGF), human mast cells reportedly do not respond to this factor. To determine if human mast cells express the NGF receptors, TrkA tyrosine receptor and the low affinity NGF receptor (LNGFR), we first analyzed the mRNA expression by RT-PCR of TrkA and LNGFR in a human mast cell line (HMC-1) and in human mast cells cultured in the presence of stem cell factor. Both HMC-1 and cultured human mast cells were found to express TrkA but not LNGFR. TrkA protein was demonstrated by Western blot analysis of HMC-1 lysates. Using flow cytometric analysis and mast cell tryptase as a mast cell marker, both HMC-1 cells and cultured human mast cells were shown to coexpress tryptase and TrkA. Treatment of mast cells with NGF resulted in phosphorylation of TrkA on tyrosine residues as detected by immunoblotting with an antiphosphotyrosine antibody. Furthermore, NGF induced the immediate early gene c-fos in HMC-1 cells. HMC-1 cells and cultured human mast cells were also found to express NGF mRNA, and conditioned medium from HMC-1 cells stimulated neurite outgrowth from chicken embryonic sensory ganglia in culture. This effect was blocked by anti-NGF. Thus, mast cells express functional TrkA and synthesize NGF, suggesting a mechanism by which NGF may act as an autocrine factor for human mast cells, and by which mast cells and nerves may interact.

Cell Communication↗
PubMed1996

Granzymes: a variety of serine protease specificities encoded by genetically distinct subfamilies.

Granzymes are a family of granule serine proteases found specifically in the cytotoxic granules of cytotoxic T lymphocytes and natural killer cells. Granzymes have features that are strongly conserved including: consensus sequences at their N-termini and around the three catalytic residues, activation from zymogenic forms, and conserved disulphide bridges. However, there is good genetic evidence to suggest that three distinct subfamilies of granzymes have coevolved. These subfamilies are most strikingly depicted by their distinct chromosomal loci and gene organization, dividing the granzyme family into subfamilies of the following: tryptases (human chromosome 5); chymotrypsin-like proteases (human chromosome 14); and a Metase amongst a cluster of elastase-like proteases (human chromosome 19). Modeling and mutational analysis has revealed that each subfamily of granzymes displays special sequence and structural features and a proteolytic specificity determined by subtle modifications to substrate binding pocket residues. It now remains of great interest to determine whether these subfamilies also possess distinct biological functions. Granzyme B has been shown to play an important role in lymphocyte-mediated target cell apoptosis and the tryptase, granzyme A, has been demonstrated to regulate the clearance of some pox virus infections. The future creation of other granzyme gene knockout mice should elucidate whether other chymotrypsin-like granzymes (C-H) also contribute to target cell apoptosis and whether the third subfamily member, natural killer cell-specific Metase, has a distinct biological function.

Amino Acid Sequence↗
PubMed2002

Embryonic hatching enzyme strypsin/ISP1 is expressed with ISP2 in endometrial glands during implantation.

Embryo hatching and outgrowth are the first critical steps on the way to a successful pregnancy. It is generally held that serine proteases are responsible for this process, although the exact mechanisms of action are not clearly understood. Recently, we described two novel implantation serine proteinase (ISP) genes that are expressed during the implantation period. The ISP1 gene encodes the embryo-derived enzyme strypsin, which is necessary for blastocyst hatching in vitro and the initiation of invasion. The ISP2 gene, which encodes a related tryptase, is expressed in endometrial glands and is regulated by progesterone during the peri-implantation period. Based on similarities between ISP2 gene expression and that of a progesterone-regulated lumenal serine proteinase activity associated with lysis of the zona pellucida, we have suggested that the strypsin related protein, ISP2, may encode a zona lysin proteinase. As tryptases naturally assemble to form tetrameric structures, we have hypothesized that ISP1 and ISP2 tetramerize to form strypsin and lysin, respectively. In this study, we demonstrate that like ISP2, the ISP1 gene is also expressed in endometrial glands and is positively regulated by progesterone during implantation. Using in situ hybridization of adjacent tissue sections, we show that the ISP1 and ISP2 genes are co-expressed within the endometrial gland. Following evidence that ISP1 and 2 can efficiently form homotetramers and heterotetramers in silico, we suggest that ISP heterotetramers may be also be secreted into the uterine lumen during the implantation period. That the embryonic hatching enzyme, may also be secreted into the uterine lumen from uterus, may provide insight into the mechanisms of hatching and implantation initiation.

Animals↗
PubMed1996

Generation of antigenic peptides by lymphocyte granule serine proteases (granzymes).

We have examined the ability of several serine proteases (granzymes) isolated from the granules of the rat natural killer cell line, RNK, to generate antigenic peptides of ovalbumin (Ova) that are capable of being recognized by Ova-specific CD8+ T cells. The mouse MHC class I-restricted cytotoxic T-cell clone, GX-1, which recognizes a trypsinized fragment of Ova in the context of H-2b, was able to lyse EL4 (H-2b) target cells in the presence of Ova and the granzymes but not in the presence of Ova or granzymes alone. Similar results were obtained using the murine Ova-specific CD8+ T cell hybridomas, RF33.70 and CD8OVA. In all cases, the T cells' responses were MHC class I-restricted as Ova:granzyme mixtures failed to mediate the lysis of the MHC-disparate target cell, P815 (H-2d). The purified rat granzyme preparations contained three distinct enzymatic specificities: asp-ase met-ase, and tryptase. Aprotinin, a protease inhibitor that only inhibits tryptase activity in vitro, completely abolished the CD8+ T-cell responses to Ova. These results, along with peptide loading studies using the RMA-S cell line, suggest that the granzyme treatment of Ova can generate the proper antigenic fragments which facilitate class I-restricted CTL responses both in vivo and in vitro. We believe that enzymes produced and released by NK or cytotoxic T cells within a tissue microenvironment may enhance the cleavage of target cell antigens as well as soluble antigens resulting in the improved uptake and processing of soluble antigens.

Animals↗
PubMed1988

The role of chymase in ionophore-induced histamine release from human pulmonary mast cells.

Human pulmonary mast cells contain the serine proteases tryptase and chymase. Chymase is present in much smaller quantities than tryptase. The definite physiological role of both enzymes remains to be elucidated, angiotensin processing has been proposed as one possible function of chymase. A dose-dependent inhibition of A 23187-induced histamine release from dispersed human lung mast cells was observed after pretreatment with diisopropylfluorophosphate (DFP) or 1-1-tosyamide-2-phenylethyl chloromethyl ketone (TPCK) but not with N-2-p-tosyl-1-lysine chloromethyl ketone (TLCK). In contrast, no inhibition was observed under the same conditions with isolated rat peritoneal mast cells. These results indicate that a chymase is probably an important factor in a late phase of human lung mast cell activation. Current work focuses on the isolation of human lung chymase to further investigate this topic.

Animals↗
PubMed1995

Phenotypic characterization of skin lesions in urticaria pigmentosa and mastocytomas.

In order to identify possible cellular abnormalities in human mastocytosis, sections from 13 urticaria pigmentosa lesions and 5 mastocytomas were compared with 5 normal skin specimens using histochemical, enzyme histochemical and immunohistochemical techniques. All toluidine blue-positive mast cells also reacted with Fc epsilon RI and c-kit antibodies, almost all stained for tryptase, many for chymase and the myeloid workshop mast cell antibodies, few for Fc epsilon RII and none for the proliferation marker Ki-67. Urticaria pigmentosa lesions contained fewer epidermal Langerhans cells and a lower percentage of avidin-positive mast cells than mastocytomas and normal skin. Mastocytomas exhibited generally weaker staining for mast cell markers and mostly lacked Fc epsilon RI-bound IgE on mast cells and Langerhans cells, although the receptor was able to bind IgE in tissue sections. Most of the mast cell antibodies also reacted with other cell types. Only toluidine blue, avidin, tryptase and chymase stains were mast cell specific. Mast cells in mastocytosis thus differed only to a minor degree from normal mast cells, although distinct pathomechanisms may play a role in urticaria pigmentosa and mastocytosis.

Adolescent↗
PubMed1988

The effect of serine esterase inhibitors on ionophore-induced histamine release from human pulmonary mast cells.

The serine proteases tryptase and chymase are present in human pulmonary mast cells. About 10-100 times more tryptase than chymase is found in these cells. However, a clear physiological role for both enzymes remains to be elucidated; angiotensin processing has been proposed as one possible function of chymase. A dose-dependent inhibition of A23187-induced histamine release from dispersed human lung mast cells was observed after pretreatment with the serine protease inhibitor diisopropylfluorophosphate (DFP) or the chymotrypsin-like enzyme inhibitor N-tosyl-L-phenylalanine chloromethylketone (TPCK) but not with the trypsin-like enzyme inhibitor N-tosyl-L-lysine chloromethylketone (TLCK). These results indicate that a chymase is probably an important factor in a late phase of human lung mast cell activation.

Calcimycin↗
PubMed1998

Anaphylactoid reaction to pentastarch.

PURPOSE: To report a probable anaphylactoid reaction to pentastarch, a low molecular weight hydroxyethyl starch (HES) colloid solution. CLINICAL FEATURES: Following a closed head injury, an 18-yr-old male was admitted to the Intensive Care Unit. Therapy was directed towards control of intracranial pressure (ICP) and maintenance of cerebral perfusion pressure (CPP). In the first 12 hr after admission, he had received 2500 ml polygeline (Haemaccel, Hoechst Marion Roussel Ltd.) and a dopamine infusion (up to 10 micrograms.kg-1.min-1) titrated to achieve a mean arterial pressure (MAP) of > or = 80 mmHg. Subsequent failure to achieve the target MAP resulted in commencement of a noradrenaline infusion (2.67 micrograms.min-1), and rapid administration of 500 ml pentastarch (Pentaspan, DuPont Pharmaceuticals). During the HES infusion, marked hypotension (MAP < 60 mmHg) developed associated with marked truncal urticaria. The hypotension was resistant to escalation of noradrenaline to 36 micrograms.min-1. Haemodynamic stability was rapidly restored and maintained with adrenaline boluses (total 450 micrograms) and infusion (1.67 micrograms.min-1). The remainder of the patient's ICU and hospital stay was unremarkable. A serum tryptase drawn in the first 40 min of the reaction was not elevated. Other biochemical markers were not assayed. Skin testing has not been carried out. CONCLUSION: The temporal relationship and clinical manifestations observed in this case, together with the resistance to inotropes/vasopressors other than adrenaline is highly suggestive of an anaphylactoid reaction to pentastarch. The diagnostic value of serum tryptase may be compromised when blood samples are drawn too early.

Accidents, Traffic↗
PubMed2001

[Occult cutaneous mastocytosis].

Mastocytosis is diagnosed without difficulty if it presents with easily recognizable lesions of urticaria pigmentosa. Recently, we have identified hardly visible skin lesions of mastocytosis in Hymenoptera venom allergic patients ("occult mastocytosis"). In addition, in approximately 15% of the patients with typical cutaneous lesions, urticaria pigmentosa was at first mistaken for other conditions and thus not linked to simultaneous symptoms of systemic mastocytosis. In most patients with unrecognized mastocytosis, the diagnosis was supported by raised basal serum tryptase levels. Cutaneous mastocytosis is often overlooked and more frequent than assumed. Measurement of basal serum tryptase concentrations can make an important contribution to the diagnosis of mastocytosis, but it does not replace a meticulous skin examination.

Bee Venoms↗
PubMed2003

Death in anaphylaxis in a man with house dust mite allergy.

Up to recently the post-mortem diagnosis of anaphylaxis has been based solely on circumstantial evidence. With the development of assays for mast cell tryptase it is now possible to verify cases of suspected anaphylaxis. Here we present one such case, which initially appeared to be due to sudden death of unknown cause. A 47-year-old farmer was found dead in his bathroom around midnight. Hospital records revealed that he had previously been diagnosed with an allergy to house dust mites. He had also had infrequent episodes of airway symptoms, nausea, hypotension and diarrhoea usually after going to bed. The forensic autopsy did not give any clue to the cause of death. Serum tryptase in post-mortem blood was found to be substantially elevated in two samples (170 and >200 microg/L). Analysis of allergen-specific IgE showed high values for Dermatophagoides pteronyssinus and farinae. High mite allergen levels were found in dust obtained from the patient's mattress. The results of the immunological tests support the assumption that he died of anaphylactic shock. The circumstances and the patient's history of previous attacks after going to bed point to the fact that exposure to mite contaminated food and/or exposure to mite allergens in bed might have caused his death.

Adult↗
PubMed1997

Effect of 3 hours of passive smoke exposure in the evening on inflammatory markers in bronchoalveolar and nasal lavage fluid in subjects with mild asthma.

OBJECTIVE: The aim of this study was to investigate the effect of environmental tobacco smoke (ETS) exposure in the evening on inflammatory changes in bronchoalveolar (BAL) and nasal lavage (NAL) fluid. METHODS: Ten subjects with mild asthma [mean (+/- SD) age, 25 +/- 2 years, FEV1% pred., 93 +/- 6%, PC20FEV1 0.44 x 5.11 mg/ml methacholine] were exposed to ETS (22.4 +/- 1.2 ppm CO) or ambient air (sham) for 3 h (7.00 to 10.00 p.m). Bronchoscopy was performed the following morning at 7.00 a.m. A visual endoscopic score was assessed, and BAL fluids were analyzed for cellular composition and concentrations of histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, tryptase, prostanoids and leukotrienes. Nasal lavages were performed 30 min prior to and 30 min after exposures, and NAL fluids were analyzed for histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, and tryptase. RESULTS: There was a significant rise in symptoms after ETS exposure compared with sham (P < 0.05). Spirometric lung function did not change during or after exposure compared with pre-session values. Visual bronchoscopic scoring revealed no significant effect of ETS exposure, nor did BAL cells and mediators or NAL mediators as compared with pre-challenge or post-sham values. CONCLUSION: In the subjects tested, a 3-h ETS exposure in the evening appeared not to have an inflammatory effect detectable in BAL or NAL fluid.

Adult↗
PubMed2003

Mast cells and tubulointerstitial fibrosis in patients with ANCA-associated glomerulonephritis.

BACKGROUND: To elucidate the role of mast cells (MCs) in the pathogenesis of crescentic glomerulonephritis, we investigated the immunohistochemical localization of MCs in the kidney and the correlation between MC localization and tubulointerstitial lesions in biopsy specimens and serum stem cell factor (SCF) levels in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis. METHODS: Thirteen patients with ANCA-associated glomerulonephritis were enrolled in this study. Clinical parameters, such as serum creatinine and urinary protein excretion, were obtained from each patient at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining, using the labelled streptavidin bio-tin (LSAB) method. Monoclonal antibodies to human tryptase, alpha-smooth-muscle actin, and CD68 were used as primary antibodies. Ten cortical interstitial fields were randomly selected at an original magnification of x400 and assessed using a computer-assisted color image analyzer. Tubulointerstitial fibrosis was assessed as the percentage of the area stained with Masson trichrome in ten cortical interstitial fields. The measurement of serum SCF levels was performed by using an enzyme-linked immunoassay. RESULTS: In all of the control subjects, a few tryptase-positive MCs were observed in the glomeruli and interstitium. In contrast, sparse MCs were observed in the interstitium, but not in the glomeruli of diseased kidneys. The number of interstitial MCs in the tubulointerstitial lesions was positively correlated with the degree of interstitial fibrosis. Moreover, a significant positive correlation was observed between the number of interstitial MCs and the serum SCF concentration (r = 0.85; P = 0.001). CONCLUSIONS: Our findings suggest that MC infiltration induced by SCF in interstitial tissues seems to be associated with tubulointerstitial fibrosis in human ANCA-associated glomerulonephritis.

Anti-Glomerular Basement Membrane Disease↗
PubMed1990

Protease-specificity of Kunitz inhibitor domain of Alzheimer's disease amyloid protein precursor.

The putative inhibitor domain of Alzheimer's disease amyloid protein precursor was purified from E. coli containing a synthetic gene encoding the Kunitz domain. The purified protein (A4 inhibitor) inhibited the activity of trypsin, forming a 1:1 molar complex with the enzyme. It also strongly inhibited plasmin (Ki = 7.5 x 10(-11) M) from human serum and tryptase (Ki = 2.2 x 10(-10) M) from rat mast cells (tryptase M). In addition, it inhibited rat pancreatic trypsin, alpha-chymotrypsin and kallikrein and human serum kallikrein, but did not inhibit rat chymase, pancreatic elastase, alpha-thrombin, urokinase, papain or cathepsin B.

Amino Acid Sequence↗
PubMed1992

Collagenase in synovitis of rheumatoid arthritis.

There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue.

Arthritis, Rheumatoid↗
PubMed1991

Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway.

To assess whether mast cell and eosinophil (EOS) degranulation occurs in the airway of subjects with moderately symptomatic asthma, we have measured levels of preformed mast cell-derived mediators (histamine and tryptase) and EOS-derived mediators (major basic protein and EOS-derived neurotoxin) in bronchoalveolar lavage fluid (BALF) obtained from patients with symptomatic (N = 14) and asymptomatic asthma (N = 9) and patients without asthma (N = 6). Both the FEV1 (1.52 +/- 0.33 L:55% +/- 15% of predicted FEV1) and the forced expiratory flow at 50% (FEF50) (1.11 +/- 0.62 L/sec:26% +/- 14% of predicted FEF50) in the patients with symptomatic asthma were significantly lower than the corresponding values for FEV1 (3.16 +/- 0.45 L:86% +/- 10% of predicted FEV1) and the FEF50 (4.04 +/- 1.54 L/sec:71% +/- 25% of predicted FEF50) in the patients with asymptomatic asthma. Levels of histamine (4.8 +/- 5.0 ng/ml versus 0.2 +/- 0.2 ng/ml) (p = 0.05), EOS-derived neurotoxin (420.6 +/- 959.4 ng/ml versus 12.6 +/- 7.7 ng/ml) (p = 0.05), major basic protein (31.4 +/- 46.6 ng/ml versus less than 9 ng/ml) (p = 0.05), and percent EOSs (10.6% +/- 7.0% versus 1.1% +/- 0.9% of BAL cells) (p = 0.0006) were all significantly elevated in BALF from symptomatic compared to asymptomatic patients with asthma. The elevated levels of tryptase (13.2 +/- 14.8 ng/ml versus 3.9 +/- 3.9 ng/ml) in BALF from symptomatic compared to asymptomatic patients with asthma approximated, but did not reach, statistical significance. Spontaneous histamine release from BAL mast cells of symptomatic patients with asthma was 46% +/- 5% compared to 5% +/- 2% in asymptomatic patients with asthma. In response to antihuman IgE, histamine release from BAL mast cells recovered from asymptomatic patients with asthma increased to 25% +/- 10%, whereas in BAL mast cells of symptomatic patients with asthma, no anti-IgE potentiation of histamine release occurred. This study suggests that mast cell and EOS degranulation is ongoing in the airway of patients with moderately symptomatic asthma.

Adolescent↗
PubMed1992

Immunohistology of the nasal mucosa in seasonal allergic rhinitis: increases in activated eosinophils and epithelial mast cells.

The immunohistology of the nasal mucosa was examined in 13 grass pollen-sensitive patients and in seven normal nonatopic control subjects before and during the pollen season. Cryostat sections (6 microns) of biopsy specimens from the inferior turbinate were immunostained with the alkaline-phosphatase antialkaline-phosphatase method and a panel of monoclonal antibodies. Mast cell subtypes were measured with a double sequential immunostaining method. Within the submucosa, seasonal increases in total (MBP+, p less than 0.01) and "activated" (EG2+, p less than 0.01) eosinophils were observed for the patients, which were significant when these counts were compared with counts for those of control subjects (MBP+ p less than 0.01; EG2+ p less than 0.001). Within the nasal epithelium, seasonal increases in total (p less than 0.05) and "activated" (p less than 0.02) eosinophils were also observed. Mast cell counts revealed seasonal increases in tryptase-only positive mast cell (MCT) (p less than 0.02) but not chymase plus tryptase-positive mast cells (MCTC) within the epithelium that were significant when counts were compared with those of control subjects (p less than 0.03). No significant changes were observed within the submucosa or epithelium for total leukocytes (CD45+ cells) or T-lymphocytes (CD3+, CD4+, CD8+, and CD 25+ cells) for either group. Similarly, no significant changes were observed for neutrophils (antielastase), macrophages (CD68+), nor HLA-DR+ cells. In the subjects with rhinitis, seasonal submucosal CD3+ counts correlated with MBP+ eosinophils (r = 0.56; p less than 0.05) and MCTS (r = 0.65; p less than 0.02). Similarly, seasonal epithelial EG2+ eosinophil counts correlated with MCTs (r = 0.56; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Interleukin-6 and interleukin-1 alpha production is associated with antigen-induced late nasal response.

BACKGROUND: Cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-6 and granulocyte macrophage-colony stimulating factor (GM-CSF) are able to potentiate allergic inflammation and seem to be implicated in the development of the late allergic reaction. METHODS: To study the time course of cytokine production, sequential lavages were performed after nasal allergen challenge. Thirteen patients with allergic rhinitis and four healthy subjects were exposed to grass pollen (n = 6 and n = 2, respectively) or dust mite allergen (n = 7 and n = 2, respectively). RESULTS: Among the patients with allergic rhinitis, a single early response (single responders) developed in four, eight exhibited a dual response (dual responders) and one patient as well as the four healthy subjects did not respond. In addition to the measurement of IL-1 alpha, IL-6, TNF-alpha and GM-CSF concentrations by ELISA, the release of histamine, tryptase, and eosinophil cationic protein was also evaluated by radioimmunoassay performed on nasal lavage fluids. Concerning mediator levels in nasal lavage fluid, neither histamine release nor cytokine elevation were noted in healthy subjects. As previously described, histamine, tryptase and eosinophil cationic protein were released in single and dual responders. Concerning cytokines, TNF-alpha was undetectable in the majority of nasal lavages and an increase in GM-CSF concentration was occasionally observed whatever the type of response. In contrast, an increase in IL-1 alpha and IL-6 levels was observed for dual responders during the early period (12.6 +/- 3 and 9.2 +/- 2 pg/ml, respectively; p < 0.01 in both cases) and at a higher level during the late period (14.5 +/- 4, p not significant and 16.7 +/- 8 pg/ml, respectively; p < 0.01) when compared with baseline values (7.2 +/- 2.2 and 2 +/- 0.7 pg/ml, respectively). For single responders IL-1 alpha and IL-6 secretion was detected mainly during the early period. CONCLUSION: These data suggest a role for IL-1 alpha in the induction and perennisation of the inflammatory reaction in allergic rhinitis, whereas the role of IL-6 remains to be investigated.

Adult↗