Masaharu Muranaka

Adjuvant activity of diesel-exhaust particulates for the production of IgE antibody in mice

The prevalence rate of allergic rhinitis caused by pollen has strikingly increased in Japan in the last three decades. The number of diesel cars in use has also rapidly increased in the country. This fact urged us to study the effects of particulates emitted from diesel cars on the production of IgE antibody. The primary IgE antibody responses in mice immunized with intraperitoneal injection of ovalbumin (OA) mixed with diesel-exhaust particulates (DEP) were higher than those in the animals immunized with OA alone. This effect of DEP on the production of IgE antibody in mice was also demonstrated when mice were immunized with repeated injections of dinitrophenylated-OA. In addition, persistent IgE-antibody response to major allergen of Japanese cedar pollen (JCPA), a most common pollen causing allergic rhinitis in Japan, was observed in mice immunized with JCPA mixed with DEP but not in the animals immunized with JCPA alone. The results do indicate that the adjuvant activity of DEP can not be excluded as a possible cause of the associated change in the number of diesel cars and allergic rhinitis caused by pollen in Japan.

Diesel-exhaust particulates inoculated by the intranasal route have an adjuvant activity for IgE production in mice

Our previous study indicated that the IgE antibody responses in mice immunized with intraperitoneal injection of the antigens mixed with diesel-exhaust particulates (DEP) were higher than those in the animals immunized with the antigens alone. We examined the adjuvant activity of DEP inoculated by the intranasal route, i.e., the natural entrance of DEP. In 3-week interval immunization, the IgE antibody responses in mice immunized with intranasal inoculation of ovalbumin (OA) mixed with DEP were higher than responses in the animals immunized with OA alone. DEP had an adjuvant activity for anti-OA IgE antibody production, even in a small dose such as 1 micrograms administered with a 3-week interval. Also in 1-week interval immunization, the enhancing effect of DEP on anti-OA IgE antibody production was demonstrated when mice were immunized with intranasal inoculation of OA and DEP. The possibility cannot be excluded that DEP, which are kept buoyant in the environmental atmosphere of urban districts, may exert an adjuvant activity for IgE antibody production after being inhaled into the human body and have some relation to the mechanism of the outbreak of allergic rhinitis caused by pollens in Japan.

IgE antibody‐mediated shock reaction caused by topical application of chlorhexidine

A case of an anaphylactic shock following topical application of chlorhexidine preparation is reported. Specific skin‐sensitizing antibodies against chlorhexidine were demonstrated in the serum from the patient by a passive transfer test. IgE antibodies against chlorhexidine were also detected by radioallergosorbent technique (RAST). Paper discs conjugated with chlorhexidine‐HSA (human serum albumin) significantly bound the IgE antibodies. Furthermore, all of the sera from seven other patients with shock reactions following the topical application of chlorhexidine preparation also showed high RAST counts. Both chlorhexidine gluconate and chlorguanide which represents approximately half a molecule of chlorhexidine inhibited the reaction in a dose‐dependent fashion. It is suggested that the shock reactions following topical application of chlorhexidine are mediated by IgE antibodies against chlorhexidine and that chlorhexidine and chlorguanide share the same antigenic determinant.

Enhancing Effect of Suspended Particulate Matter on the IgE Antibody Production in Mice

Suspended particulate matter (SPM), suspended in the polluted environmental atmosphere, are perpetually inhaled into the human body and are considered to have profound effects on human health. This study investigated the enhancing effect of SPM on the IgE antibody production in mice. The IgE antibody responses in mice immunized with intranasal administration of ovalbumin (OA) plus SPM at 3-week intervals were higher than responses in the animals immunized with OA alone. When the dose of OA administered as an antigen was 0.25 microgram, the time course and magnitude of enhancement by SPM was comparable to those by killed Bordetella pertussis, a common adjuvant. SPM had an enhancing effect on IgE antibody production even in a small dose such as 0.25 microgram administered at 3-week intervals. The possibility cannot be excluded that the natural exposure of humans to SPM in the environmental atmosphere may explain the high prevalence rate of allergic rhinitis caused by pollens in polluted districts in Japan.

Topical thrombin-induced IgE-mediated anaphylaxis: RAST analysis and skin test studies☆

Bovine topical thrombin (BTT) is a heterologous plasma thrombin concentrate that has been frequently used for the hemostasis since the 1940s. Recently, three patients in Japan went into shock after the topical application of BTT at lesion sites, and two of these patients had received BTT repeatedly. The clinical symptoms and the increased anti-BTT percent RAST counts suggest that these reactions were shock mediated by anti-BTT IgE antibodies. The RAST-inhibition analysis suggested that the antigenic substance(s) were bovine-specific moiety(ies) mainly involved in the contaminant rather than bovine thrombin itself. The skin tests were studied to predict such allergic reactions. The intracutaneous test provoked nonspecific reactions even at the low concentrations of BTT. The prospective study on the predictive value of the prick test with 1000 U/ml (1 mg/ml) of BTT in 192 patients suggested that it is useful to detect highly sensitive patients. In addition, the increased levels of anti-BTT IgE antibodies in patients 1 month after the single administration of BTT suggested the immunogenicity of the topical application of BTT.

Bronchial responsiveness to acethylcholine in patients with bronchial asthma after long-term treatment with gold salt

Three groups of adult patients with bronchial asthma were subjected to long-term chrysotherapy (gold therapy), immunotherapy, or symptomatic therapy. Five of 14 patients who were treated with repeated injections of gold salt entered a symptom-free state that continued for more than 3 yr without the use of any bronchodilators or corticosteroids. In the other groups, there were no patients who entered such a state of long-term remission during the treatment. A statistically significant decrease in the bronchial responsiveness to inhaled acetylcholine was also observed in patients who received chrysotherapy. In the other groups, there were no significant differences between the bronchial responsiveness to acetylcholine that was estimated before the treatment and that measured after long-term treatment. Long-term chrysotherapy in the asthmatic patients did not reduce their serum level of total IgE. Gold salt, which is generally accepted as an antirheumatic drug, has also been used as an antiasthmatic drug by some Japanese practitioners despite the absence of evidence to support the therapeutic effect of the drug on asthma; the results of the study provide more information on the treatment of bronchial asthma with gold therapy.

Bronchial reactivities to acetylcholine and IgE levels in asthmatic subjects after long-term remissions

Serum IgE concentrations, IgE antibody titers to mite allergen, the number ofblood cosinophils, the number of positive scratch tests, and the bronchial reactivity to acetylcholine were examined on the following 3 groups: (1) asthmatic subjects who had been in remission for 3 years or more; (2) asthmatics currently having asthma attacks; (3) normal healthy control subjects. Mean values were all higher in the asthmatic groups than in the controls. Differences between the 2 asthmatic groups were insignificant except for the acetylcholine inhalation tests, in which asthmatics in remission had lower bronchial reactivity than active asthmatics. In the former group, decreases in bronchial reactivity to acetylcholine after remission were observed in 7 of the 9 subjects. No correlation was obtained between bronchial reactivity and serum IgE. Of 7 asthmatics in remission having high serum IgE levels, 6 showed low bronchial responsiveness to acetylcholine, while the remaining one retained marked bronchial hyperreactivity. These results indicated that the atopic disposition of asthmatic subjects persisted but the bronchial reactivity to acetylcholine might decrease after long-term remission.

Cefotiam-induced IgE-mediated occupational contact anaphylaxis of nurses ; case reports, RAST analysis, and a review of the literature.

Cefotiam (CTM) is one of the most popular cephem antibiotics in Japan. Recently we experienced two cases of nurses with CTM‐induced contact anaphylaxis. When they were preparing drip infusions of antibiotics or working around other nurses doing so, they suddenly fell into shock with other symptoms such as flushing, urtiearia, abdominal distress, vomiting, dyspnoea and or loss of consciousness. The symptoms never occurred after they avoided exposure to CTM. Passive cutaneous or open patch tests were positive for CTM. Histamine release was induced by CTM from washed leucocytes. RAST analysis using CTM‐human serum albumin‐coupled dises showed high % RAST count, suggesting that these reactions were mediated by IgE antibodies. A RAST inhibition test suggested that the methyl‐thiotetrazol side‐chain was the main antigenic determinant. Both patients had hand dermatitis that had appeared preceding the episodes of anaphylaxis. Although the dermatitis had been resistant to treatments, it also disappeared after they avoided exposure to CTM, It seemed likely that it was also induced or exacerbated by CTM and facilitated the penetration of CTM to cause anaphylaxis. The literature is also reviewed.

Elicitation of homologous passive cutaneous anaphylactic reactions by a benzylpenicillin preparation

Abstract Four out of five commercially available benzylpenicillin preparations elicited homologous passive cutaneous anaphylactic (PCA) reaction in sensitized guinea pigs with anti-benzylpenicilloyl (anti-BPO) reaginic sera. The same preparations could not evoke PCA reaction in sensitized guinea pigs with anti-BPO γ 1 homocytotropic antibodies. The PCA reactions were completely inhibited by a prior injection of BPO-e-aminocaproic acid (BPO-EACA). Chromatographic analysis of one of the benzylpenicillin preparations on Sephadex G 10 revealed that the reagin-mediated PCA reaction was not evoked with the fractions from the main peak of the benzylpenicillin but with fractions eluted earlier. None of the fractions gave positive γ 1 -mediated PCA reactions. These results indicated that some commercial benzylpenicillin preparations contained minute amounts of the impurities that could elicit the homologous PCA reaction in guinea pigs sensitized with anti-BPO reaginic sera. It was also indicated that the PCA elicitation activity of the benzylpenicillin preparation in the system of reagin-mediated PCA differed from that of γ 1 -mediated PCA.

Gold-induced reduction in reactivity to histamine in isolated guinea pig tracheal rings

Direct effects of gold preparations on the smooth muscle were investigated on isolated guinea pig tracheal rings. Pretreatment of the tracheal rings for 150 min with 100 microM of gold sodium thiomalate [Au(I)] significantly reduced the contraction heights induced by 4.5 microM histamine from 0.24 +/- 0.02 to 0.14 +/- 0.01 g (p less than 0.01). Gold chloride [Au(III)] was far more potent in its inhibitory effects than gold sodium thiomalate. With 15 min preincubation, gold chloride significantly suppressed the histamine-induced contraction (p less than 0.05) at such a low concentration as 10 microM (3.4 micrograms/ml). Gold chloride as well as gold sodium thiomalate did not interfere with the ciliary motion of the tracheal epithelium, whereas colchicine, having no effect on the histamine-induced contraction, did interfere with ciliary motion. These results reveal that gold itself inhibits noncaustically the guinea pig tracheal contraction induced by histamine.