Attenuation of allergen sensitivity early in the course of ragweed immunotherapy.

During the course of an open immunotherapy (IT) study of ragweed (RW)-allergic patients, nasal mediator release was studied by provocation testing. All subjects had a history of seasonal RW rhinitis, positive skin puncture test to RW, and RW-specific IgE by RAST. Nasal challenge was performed with serial dilutions of RW extract, before and after 12 weekly injections, providing a cumulative dose of 0.22 microgram of Amb a I. Serum IgE and IgG and basophil histamine release with RW were also measured. By 12 weeks of IT, when only 1% of the usual maintenance level dose had been administered, mean histamine release and TAME-esterase activity in nasal washes decreased significantly (p less than 0.05 and p less than 0.01). Prostaglandin D2 release did not change. Skin sensitivity decreased (p less than 0.05), whereas RW-specific IgE increased (p less than 0.05). No significant change in basophil histamine release was observed for RW or a control antigen. Only six of 40 subjects had an RW-specific IgG rise greater than 0.05 microgram/ml. Changes in nasal sensitivity did not correlate with the increases in IgE or IgG or with the change in skin test sensitivity. These present data indicate that there is a significant decline in nasal sensitivity to inhaled RW very early in the course of IT. There is, however, no indication of a relationship between the decreased nasal sensitivity and the production of RW-specific IgG antibodies.

[A long-term therapeutic experience with Cernilton in chronic prostatitis].

Thirty-two patients with chronic prostatitis were given 6 tables of Cernilton daily for 12.6 weeks on the average. Improvement of subjective symptoms and objective findings was noted in 74.2% and 65.6% of the cases, respectively. The effective rate was 75.0%. No subjective symptoms or abnormal changes in laboratory data were observed in any case after Cernilton medication.

High dose grass pollen tablets used for hyposensitization in hay fever patients. A one-year double blind placebo-controlled study.

Previous, placebo-controlled clinical trials with oral hyposensitization in grass pollinosis have been disappointing. Since the results possibly could be explained by too low doses of ingested allergens, the present study was initiated to evaluate the effect of high doses of allergens. Forty-two adults with symptoms in the grass pollen season and with grass pollen sensitivity demonstrated by skin prick test and conjunctival provocation test were included. Enterosoluble tablets were administered daily for 1 year. Twenty-two patients, who completed the study, received placebo and 17 mixed grass pollen allergens from rye grass, timothy grass, cultivated rye and velvet grass. Evaluated either by self-assessment or by symptom and medicine score before and after treatment, the group receiving pollens did not improve clinically compared the controls. During the study, conjunctival sensitivity decreased equally in the two groups, and changes in specific IgE, allergen-induced histamine release from blood cells and skin prick test were insignificant and with no difference between groups. Five patients, who received pollen allergens, had episodes of urticaria or angioedema, and a further three patients on the same treatment had slight gastrointestinal side effects. In conclusion, enterosoluble grass pollen allergens in contrast to birch pollens did not have any therapeutic effect, even in doses more than 4,000 times higher than those used for subcutaneous hypersensitization. The reason may be degradation of allergens before the immune system is reached.

Suppression of murine IgE responses with amino acid polymer/allergen conjugates. IV. Suppressive activities in established IgE model systems.

Conjugates of poly-N-methylglycine (polysarcosine) and grass pollen extracts, previously found to be capable of suppressing immature IgE antibody responses in mice, were shown to be highly effective at inhibiting the capacity of immune splenocytes to produce a secondary response in sub-lethally irradiated recipient animals. Anamnestic IgE responses in mice primed without adjuvant were also suppressed, but the effects were modest and of short duration. The predictive value of murine models for selecting clinically appropriate specific IgE suppressive agents and treatment schedules that might be successfully employed for clinical use are discussed.

Effect of drugs on the increase in cell numbers in the peritoneal cavity of the actively sensitised mouse after intraperitoneal challenge with antigen.

The injection of antigen into the peritoneal cavity of actively sensitised mice produced an increase in the number of neutrophils in peritoneal washings collected 4 h later but after 1 day the numbers had returned to control levels. The increase in numbers of mononuclear cells and eosinophils in the peritoneal washings peaked at 2 days and persisted for at least 5 days. Dosing the mice with phenidone, a dual inhibitor of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism, potentiated the neutrophil infiltration at 4 h but had no significant effect upon the subsequent mononuclear cell and eosinophil infiltration. In contrast, treatment with the corticosteroid, dexamethasone, reduced the infiltration by all three types of cells, providing further evidence that the corticosteroids can inhibit immune-induced cellular infiltrations by mechanisms other than the inhibition of arachidonic acid metabolism. Isoprenaline, given to the mice before antigen challenge, had no effect on the subsequent neutrophil infiltration, but repeated doses did inhibit the mononuclear cell and eosinophil infiltration measured 4 days later. Aminophylline, disodium cromoglycate and cyproheptadine had no effect upon the cellular changes.

[Clinical evaluation of cernilton in the treatment of the benign prostatic hypertrophy].

Cernilton was given clinically to 30 patients with benign prostatic hypertrophy. Cernilton was given orally at least for 12 weeks at a daily dose of 6 tablets in three divided doses. The overall clinical efficacy on subjective symptoms was 80%, and that on objective signs, 43%. During the administration period of Cernilton, no serious untoward effects were observed in either the clinical or laboratory findings. It is, therefore, suggested that, from the clinical point of view, Cernilton is a useful and safe drug in the treatment of benign prostatic hypertrophy.

Local nasal immunotherapy: efficacy of low-dose aqueous ragweed extract.

In previous studies preseasonal local nasal immunotherapy (LNIT) with moderate doses of aqueous ragweed extract (mean total dose 59 micrograms of AgE and 139 micrograms of AgE) was an effective treatment for ragweed hay fever; however, local adverse reactions during therapy were common. This study evaluated the clinical and immunologic responses to LNIT by use of lower doses of aqueous ragweed extract in order to minimize these adverse reactions. Patients were administered preseasonal LNIT for 7 wk and received a mean total dose of 4.7 micrograms of AgE. During the ragweed season, symptom/medication scores (SMS) of the treated patients were equivalent to SMS of untreated patients. Serum ragweed-specific IgE and nasal secretory ragweed-specific IgA rose slightly in the treated patients but not to the extent observed in previous studies. After the ragweed season treated and untreated patients had a substantial increase in serum ragweed IgE antibody titers. No correlation could be found between antibody responses and SMS. This study indicates that LNIT with lower doses of aqueous ragweed extract is clinically ineffective.

The protective effect of pollen extracts against allyl alcohol damage of the liver.

In male Wistar rats the hepatoprotective effect of pollen extracts (Cernitins) agains. orally introduced 1% allyl alcohol (0.4 ml per 100 g body weight) was investigated Cernitins were applied orally at 0.6, 24 and 30 h after allyl alcohol administration. After 48 h an autopsy was performed and blood was collected for biochemical tests. Liver damage was evaluated by measurement of aminotransferases (AspAT, AlAT) and alkaline phosphatase activity, total bilirubin level in the blood serum as well as by histological examination of the livers. Cernitins significantly reduced the serum enzymes elevations induced by allyl alcohol. The hepatoprotective properties of Cernitins were confirmed by histopathological studies.

The effect of short-term immunotherapy with Pollinex on anti-IgE and antigen-induced histamine release from sensitive human basophils.

Anti-IgE and antigen-induced histamine release from basophils isolated from 30 atopic patients sensitive to grass pollen allergens was evaluated. The studies were made before and after short-term immunotherapy with glutaraldehyde-pollen-tyrosine adsorbate (Pollinex). It was shown, that after immunotherapy a significant drop in anti-IgE and specific antigen-induced histamine release from isolated basophils occurs. The investigations confirm that the diminution of the target cell sensitivity and releasability may be one of the effects of specific immunotherapy.

Allergen-controlled study of intranasal immunotherapy for ragweed hay fever.

Previous studies of intranasal immunotherapy have not included control groups treated with an irrelevant allergen. In the present double-blind study, we tested the effectiveness of intranasal immunotherapy in 20 patients sensitive to both short ragweed (SRW) and orchard grass (OG). Patients sprayed increasing concentrations of either SRW (n = 11) or OG (n = 9) extract intranasally six times per day for 8 wk before the SRW pollination season. The effects of this treatment were determined by analysis of symptom score diaries and clinical examinations during the SRW pollination season. SRW-treated patients received cumulative AgE doses from 3 to 59 micrograms (mean 21); this mean dose was approximately sevenfold less than that used in a previous study from our laboratory. All patients reported immediate hay fever symptoms after use of the nasal spray. Five patients (four SRW- and one OG-treated) reported episodes of mild epistaxis during treatment; no other unexpected side effects were noted. During the treatment period, more SRW-treated patients showed signs of nasal obstruction and edematous nasal mucosa than OG-treated control patients (p less than 0.03). During the SRW pollination season, the SRW-treated patients reported lower mean weekly symptom scores than the OG-treated control patients, but the difference was not statistically significant. Supplemental antihistamine use was significantly higher (p less than 0.016) in the OG-treated control patients during the SRW pollination period. Subjective assessment of treatment efficacy by patients was similar in both treatment groups. We conclude that intranasal immunotherapy was of only marginal benefit in this study.

Controlled evaluation of allergoid in the immunotherapy of ragweed hay fever.

Immunotherapy with ragweed allergoid administered in a clustered regimen, placebos in a clustered regimen, and unaltered ragweed extract (allergen) in a weekly regimen were compared in three groups of hay fever patients carefully matched for ragweed sensitivity. The allergoid and placebo comparison was performed double-blind and the unaltered ragweed extract comparison was single-blind. In terms of antigen E (AgE) equivalents, doses were about 50 times higher in the allergoid-treated group than in the allergen-treated group. Whereas there was no immunologic response to placebos, the allergoid regimen produced a more rapid serum IgG antibody response, with significantly higher posttreatment levels than those in the allergen regimen. Initial IgE antibody rises and subsequent slow declines were similar. Symptom-medication scores were similar in the two specifically treated groups and significantly less than scores reported by the placebo group (p less than 0.01). Due to an overestimate of the initial allergoid doses, systemic reactions occurred mostly in the early visits with allergoid treatment, whereas systemic reactions appeared late in the allergen treatment. The overall incidence was similar. In a second year, after 8 mo of no injections, a preseasonal booster regimen with both materials produced virtually no untoward reactions. During the period of no injections, IgG antibody declines were modest and, after boosters, IgG antibody levels rose promptly. Clinical results in both groups were again excellent, with an advantage for allergoid.