Walter Dorsch

Mediator studies in skin blister fluid from patients with dual skin reactions after intradermal allergen injection

Skin blister fluid (SBF) samples obtained after allergen skin testing in a total of 26 patients with late cutaneous reactions (LCRs) were examined for the presence of various vasoactive mediators. Histamine was predominant during the early phase of the wheal and flare reaction(206 +/- 40 ng/ml) and decreased with the development of the LCR toward normal SBF levels (around 20 ng/ml). Kallikrein activity was measurable in low amounts (around 5 ng/ml) in three out of 13 SBF samples taken 30 min after skin testing and in five of 13 SBF samples taken 6 hr after allergen testing. The thromboxane B2 content of SBF showed an increase with the development of LCR (control skin 976 +/- 483 ng/ml; allergen-tested skin 30 min after allergen injection, 1465 +/- 1566 ng/ml; allergen-tested skin 6 hr after antigen injection, 1775 +/- 731 ng/ml). SBF obtained from normal skin as well as from allergen-tested skin showed significant platelet-activating property as measured in an in vitro serotonin-release assay from washed human platelets. It is concluded that during the development of late-phase reactions a complex interaction of various mediator systems takes place.

Induction of late cutaneous reactions by skin-blister fluid from allergen-tested and normal skin

Ten healthy volunteers (five atopic, five nonatopic) and seven patients suffering from allergic bronchial asthma and rhinitis/conjunctivitis as well as showing dual reactions after intradermal or bronchial allergen challenge were investigated. Using the suction blister technique, we obtained skin-blister fluid (SBF) from dual skin reactions 30, 60, 180, and 300 min after allergen injection and from normal untested skin. The biologic activity of SBF was tested by intradermal reinjection of the fluid into the donor. SBF taken from dual skin reactions 30 or 60 min after allergen injection produced late cutaneous reactions (LCRs) quite similar to those induced by the allergen. SBF taken from LCR areas 180 or 300 min after antigen testing had much weaker effects, similar to SBF from untested skin. A possible content of allergen extract in SBF from allergen-tested skin areas was not responsible for the observed effects as demonstrated in passive cutaneous anaphylaxis experiments in monkeys. High doses of SBF from untested skin were able to induce LCRs similar to but weaker than LCRs produced by SBF taken at early phases from dual skin reactions. Similar volumes of autologous heparin-plasma or serum did not induce LCRs. It is concluded that during the initial phase of dual skin reactions, factors are formed that are able to induce LCRs. The generation of these mediators seems to be caused at least in part by the extravasation of plasma.

Histamine and Allergic Diseases

Although known for almost 80 years, histamine (H) (β-imidazolylethylamine) still remains a fascinating substance for many researchers. In spite of great progress in knowledge of pharmacology and release mechanisms as well as the discovery of other potent mediators, the definition of the physiological role of histamine in health and disease remains incomplete. The role of H — among others — as mediator of immediate-type hypersensitivity diseases (both allergic and pseudo-allergic in origin) is rather well established. This proinflammatory effect involves predominantly H1 receptors on mucosal cells, smooth muscle and vascular endothelium. Similarly well-defined is the H2-mediated role of H in gastric acid secretion. Less well defined is the clinical relevance of cardiac H1 and H2 receptors (atrial H1 receptors mediating negative dromotropic effects, while ventricular tachycardia is mediated by H2 receptors) as well as the role of H as neurotransmitter in the human brain.

Effect of Topical Indomethacin on Allergen‐Induced Dual Skin Reactions

Twelve asthmatics with dual bronchial and skin reactions after allergen challenge received topical treatment with a 5%‐indomethacin cream half an hour before and up to 7h after intradermal allergen and histamine injections. The erythema during the first 20 min of the wheal and flare reaction (WFR) was not affected, neither were the diameters of wheals and flares. 40 to 60 min after injection we observed a marked reduction of the erythema in histamine‐and allergen‐tested skin areas of 10 Patients. This effect lasted up to the 5th h alter injection of high allergen doses. During the hilly developed late cutaneous reactions (LCR) no effect 0f indomethacin on the erythema was observed, the edema of LCR was only insignificantly reduced. These results suggest that the erythema in LCR between the 1st and 4th is caused, at least in part, by local formation of prostaglandins.

Comparison of histamine release and prostaglandin E2 production of human basophils in atopic and normal individuals

SummaryThe influence of arachidonic acid (AA) metabolism upon histamine release (HR) from human basophils after stimulation with anti-IgE was studied in 23 atopic and 11 normal individuals. HR occurred significantly faster in atopics than in normals; the total amount of HR after a 40 min incubation period was not significantly different between the two groups. Indomethacin and acetylsalicylic acid (ASA) increased the quantity of HR significantly both in atopics and normals without influencing the time course. Addition of exogenous PGE2 decreased HR; here atopics were more affected than normals 5 and 10 min after challenge with anti-IgE. Production of PGE2 after stimulation with anti-IgE was very low in both groups (in the range of 30–50 pg/106 cells) and often below detection limit (10–20 pg/ml). Addition of glutathione (GSH), a coenzyme of PGE2-isomerase, increased PGE2 production 2 to 5-fold during stimulation with anti-IgE. These data support the idea that arachidonic acid metabolites play an important role in modulating the “releasability” of human basophils. It is suggested that the basophils of atopic individuals may release their histamine faster than normals — perhaps on the basis of a more slowly acting endogenous feedback mechanism by PGE2. Both phenomena support the idea of an altered “releasability” of basophils from atopics compared to normals.

Levels of Complement Factors in Human Serum during Immediate and Late Asthmatic Reactions and during Acute Hypersensitivity Pneumonitis

In 16 asthmatic patients and in four subjects suspected of having hypersensitivity pneumonitis, serum levels of CH50, C3, C4, C5 and factor B were measured before, between 10 and 20 min, between 5 and 7 h and, in the latter group, also 24 h after allergen challenges provoking type I bronchial reactions or acute hypersensitivity pneumonitis.

Antiasthmatic Effects of Onions

Thiosulfinates are responsible for antiasthmatic and anti-inflammatory properties of onions. We tested the effect of diphenylthiosulfinate on platelet-activating factor (PAF)-induced bronchial hyperreactivity to histamine: According to a randomized crossover protocol, groups of 14 guinea pigs inhaled histamine, were then treated orally with either vehicle or with 10–100 mg/kg diphenylthiosulfinate, inhaled 1 µg PAF, and thereafter the same histamine dose given prior to PAF. In the control group the histamine response increased threefold; in the treated group the histamine response decreased. The effect of 100 mg diphenylthiosulfinate lasted 12 h. Antihistamine effects were not demonstrable in this test system. We conclude that thiosulfinates inhibit PAF-induced hyperreactivity.

Komplementärmethoden oder so genannte Alternativmethoden in der Allergologie

ZusammenfassungDie Liste unkonventioneller medizinischer Techniken, die in Deutschland Anwendung finden, ist sehr lang. Sie umfasst Methoden zur Diagnostik sowie Methoden zur Therapie. Nur wenige sind als seriöse Verfahren zu bezeichnen, die klassische Methoden der Allergologie sinnvoll ergänzen können: Atemtherapie, Akupunktur, autogenes Training, Balneotherapie, funktionelle Entspannung, Klimatherapie, seriöse Diätetik, Ernährungstherapie, Phytotherapie, Physiotherapie, Psychotherapie.SummaryA lot of unconventional methods are offered to allergic patients in Germany. Only few can be considered as serious complementary methods to be used in addition to classic methods: acupuncture, balneotherapy, breathing techniques, clima therapy, relaxation techniques, some forms of dietetics, phytotherapy, physiotherapy, psychotherapy.

Effect of 15-Hydroxyeicosatetraenoic Acid (15-HETE) on Anti-Immunglobulin E- and Calcium Ionophore-Induced Histamine Release from Human Leukocytes

15-Hydroxyeicosatetraenoic acid (15-HETE) was prepared by soybean lipoxygenase-mediated oxygenation of arachidonic acid to 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and subsequent reduction by Na

IgE and common allergic diseases: Studies on pathogenesis and pharmacotherapy of late phase reactions

Late phase reactions (LPR) have generally been considered as Arthus phenomenon (type I11 allergy according to Coombs and Gell). IgE-antibodies, however, are able to initiate not only immediate (WFR), but also late cutaneous reactions (LCR). Using the skin blister technique we could show LCR to be provoked by inflammatory mediators generated during the WFR. Histamine, active kallikrein, leukotrienes, thromboxanes and platelet activating property were demonstrable in dual skin reactions. The concentation of these mediators in skin blister fluid was in part related to the time course of skin reactions. LCRs were diminished by eicosatetranoic acid, not by indomethacin, by dazoxiben ( = thromboxane synthetase inhibitor) as well as by ethanolic onion extract. Such betamimetics as salbutamol and anticholinergics as ipratropiumbromide reversed late bronchial reactions (LBR), and besides disodium cromoglycate, ethanolic onion extract could prevent LBR. In guinea pigs we could show certain oily fractions to be the carriers of the antiasthmatic effects of onions. They act at least in part by counteracting the effects of platelet activating factor. We conclude: An IgE-dependent mast cell degrada t ion can initiate not only immediate (anaphylactic), but also late reactions. They have to be distinguished from classical type I11 hyperergic reactions. IgE-dependent late reactions are maintained by a complex interaction of mediators. They represent the pathogenetic background of, e .g. long-lasting asthmatic conditions. Studies on their pathogenesis and pharmacotherapy will provide new possibilities in the treatment of common allergic diseases. Histo y/introduction