Effects of cyclosporine and dexamethasone on IgE antibody response in mice, and on passive cutaneous anaphylaxis in the rat

The suppressive effects of cyclosporine A (CsA) and dexamethasone (Dxt) on antigen-specific IgE responses to ovalbumin (OA) were studied in BALB/c mice. The effects upon other isotypes were also analyzed. The antiovalbumin IgE response did not change when low doses of CsA [8 mg/kg intraperitoneally (i.p.)] were administered; IgA also remained unchanged, while IgG and IgG1 decreased significantly. At higher CsA doses (16 mg/kg i.p. or orally), a decrease was noted for all the ispotypes assayed. Dxt administered orally at 0.3 mg/kg selectively inhibited IgE and IgA but did not influence IgG or IgG1 levels. Delayed hypersensitivity reactions to OA were not modified by CsA, but were depressed by Dxt. Although CsA had not effect on passive cutaneous anaphylaxis in the rat, Dxt significantly reduced this reaction when it was administered 6 h before challenge. These results suggest that Dxt has more specific antiallergic activity than CsA.     

SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development

BACKGROUND: Bronchial asthma is characterized by a TH2 type immune response, chronic inflammation of the airways and increased airway responsiveness. The relationship between IgE- and inflammatory-dependent mechanisms that contribute to bronchial asthma are not well defined. OBJECTIVE: The purpose of this study was to compare and analyse the immune pathways that resulted in development of allergen-induced and/or inflammatory dependent increased airways responsiveness. RESULTS: BALB/c and C57BL/6 mice responded to OVA-sensitization with elevated allergen-specific IgE/IgG1 serum antibody-titres and the development of cutaneous immediate-type hypersensitivity reactions. Increased airway responsiveness was observed following airway allergen challenges. However, the inflammatory component of the lung differed between the strains. In OVA-sensitized BALB/c mice a marked increase in lymphocytes, eosinophils and neutrophils in BAL fluids was parallelled with elevated production of IL-4, IL-5 and TNFalpha in the lung. In contrast in OVA-sensitized C57BL/6 mice, the inflammatory immune response in the lung was much weaker. We postulate that two pathways can regulate the induction of increased airway responsiveness. One depends on the presence of allergen-specific IgE/IgG1 and allergen, and a second is mediated by allergen-independent inflammation of the lung. To test this hypothesis, BALB/c mice were treated nasally with low doses of bacterial superantigen (SEB) as a prototypical inducer of airway inflammation, following which influx of lymphocytes, eosinophils and neutrophils into the airways was parallelled by development of increased airway-responsiveness in the absence of allergen-specific IgE/IgG1 antibodies and allergen. CONCLUSIONS: These results indicate that increased airway responsiveness is associated with different immunological phenotypes in BALB/c and C57BL/6 mice.     

Airborne house dust elicits a local lymph node reaction and has an adjuvant effect on specific IgE production in the mouse

Indoor suspended particulate matter (SPM) consists of many different types of particles, the vast majority of which are less than 2.5 microm in diameter. An important question is how these particles, being inhalable, contribute to asthma and respiratory symptoms. One possibility is that these particles have an adjuvant effect on the immune response and increase the IgE production, or cause a non-specific irritation in the airways, contributing to bronchial hyper-responsiveness. In this study, the adjuvant activity of indoor SPM on the response to the model allergen ovalbumin (OA) in BALB/c mice was investigated, using the popliteal lymph node (PLN) assay. The adjuvant activity on the local lymph node response was determined by measuring the PLN weight, cell numbers and cell proliferation, and the adjuvant activity on the IgE production by measuring the levels of serum IgE specific to OA. SPM was found to give a significant PLN response, both when injected alone and together with OA. SPM was also found to enhance the production of specific IgE to OA when injected together with OA, after reinjection with OA, compared with immunisation with OA alone.     

Liposome entrapped allergen reduces plasma histamine in sensitized mice

Immunotherapy of allergic diseases is associated with problems of adverse systemic reactions. We have shown earlier that liposome entrapped allergen (LEA) is effective in inducing IgG response and restricting IgE response in immunized mice. This mode of treatment may be more effective and safer if it can prevent anaphylaxis. To determine this feature, mice were administered allergen preparations repeatedly and later challenged with the same allergen. Mice given liposomal preparation showed lower specific IgE response as compared to the mice given free allergen or alum adsorbed allergen of Artemisia scoparia. Specific IgG response was higher in mice immunized with LEA. The mice immunized with liposomal preparation survived whereas others injected with free allergen or alum adsorbed allergen died probably due to anaphylaxis. High levels of histamine were observed in mice injected with free allergen as compared to the mice injected LEA. The increase in plasma histamine level may be the cause of anaphylaxis during allergen challenge. In conclusion, LEA could be used as a safe and effective mode of immunotherapy for allergy diseases, since it reduces plasma histamine levels considerably thereby reducing the chances of anaphylaxis.     

Influence of neoadjuvant chemotherapy on serum tumor markers CA 15-3, MCA, CEA, TPS and TPA in breast cancer patients with operable disease

The mycelial mass of the fungus Polyporus Squamosus strain 64 (PS-64) was disintegrated by mechanical and ultrasound treatments. After centrifugation, the supernatant containing the disintegrate was dialyzed and lyophilized. The resultant PS-64 extract was subsequently investigated as an immunomodulator of IgE and IgG responses to ovalbumin (OA) in (CBAxC57BL/6)F1 mice using passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA), respectively. Multiple injections of PS-64 extract in doses of 1.5, 15, and 150 mg/kg administered before the primary or secondary immunization of mice with OA resulted in a dose-dependent inhibition of both IgE and IgG antibody responses to OA. In contrast to the inhibition of the anti-OA IgE response noted during the entire 3-week observation period, the anti-OA IgG response was restored to control level by the third week of secondary immunization. The glass microfiber-based whole blood histamine release assay demonstrated that various concentrations of the PS-64 extract did not influence histamine release induced either by anti-IgE or by specific allergens from basophils derived from whole blood of allergen-sensitized patients. Using the hemolytic plaque assay, significant suppression of IgM-secreting cell formation was noted in (CBAxC57BL/6)F1 mice administered various doses of the PS-64 extract before immunization. The PS-64 extract inhibited the in vitro proliferation of human mononuclear cells upon stimulation with phytohemagglutinin (PHA). In a dose-dependent manner, the PS-64 extract also inhibited delayed-type hypersensitivity reaction and skin graft rejection, similar to the effect noted with usage of Cyclosporin A (CsA) in (CBAxC57BL/6)F1 mice. Our investigation suggests that the immunomodulatory effects of PS-64 should be studied further for potential clinical therapeutic utility.     

Expression of E- and P-cadherin during tooth morphogenesis and cytodifferentiation of ameloblasts

The mechanism of hyposensitization in bronchial asthma has not been fully elucidated. We established a hyposensitization model of bronchial asthma in rats and examined airway responses and immunological parameters. Brown Norway rats were sensitized by a subcutaneous injection of ovalbumin (OA) at day 1 and by the inhalation of 2% OA aerosol at day 15. Animals were hyposensitized by intraperitoneal injections of OA from day 17 to day 22. They were challenged with OA or acethylcholine (Ach) aerosol at day 23 and changes in intratracheal pressure were recorded. Lungs were lavaged and OA-induced proliferative responses by blood lymphocytes were examined for animals without aerosol challenge at day 23. OA-specific serum IgE levels were measured by enzyme-linked immunosorbent assay. Hyposensitization significantly reduced the OA-induced immediate airway response, accumulation of CD4+ lymphocytes and eosinophils recovered by bronchoalveolar lavage, and the OA-induced proliferative response by blood lymphocytes. The airway responses to Ach and serum OA-specific IgE levels in hyposensitized group were not significantly different from those in the sensitized group. These results indicate that amelioration of airway inflammation and hyporesponsiveness of lymphocytes against OA are involved in the attenuated immediate antigen-induced airway response following hyposensitization.     

Characterization of cytokine production in murine Trypanosoma cruzi infection by in situ immunocytochemistry: lack of association between susceptibility and type 2 cytokine production

The ability of subcutaneous pretreatment with an immunogenic peptide derived from Fel d I, the major cat protein, to suppress the development of allergic responses was examined in a mouse model of antigen-induced sensitization. BALB/c mice exposed to aerosolized Fel d I chain 1 peptide developed antigen-specific IgE responses, immediate cutaneous reactivity to the peptide, and increased airway responsiveness (AR). Both subcutaneous and intraperitoneal administration of the peptide prior to sensitization caused a 50% reduction in cutaneous reactivity which was associated with a decrease in serum anti-Fel d I chain 1 IgE and IgG1 antibody responses and an increase in specific IgG. Pretreatment with the peptide also suppressed spleen and lymph node proliferative responses to the peptide. However, only subcutaneous peptide injections could prevent the development of increased AR. Transfer of spleen cells from subcutaneously peptide-treated mice to sensitized recipients reduced serum antigen-specific IgE and IgG1 antibody responses and skin test reactivity, and prevented alterations in AR. These data suggest that IgE (and IgG1) responses and airway hyperresponsiveness induced by allergen sensitization via the airways can be modulated by subcutaneous administration of peptide. Further, the results define a model for investigating the modulatory effects of subcutaneous administration of immunogenic peptides or protein on an ongoing allergic response.     

Effect of pharmacist''s instruction on the treatment of asthmatics with inhaled steroid

BACKGROUND: The clinical efficacy and safety of local nasal immunotherapy (LNIT) with lyophilized 'macronized' powder has been demonstrated. However, the immunological changes possibly induced by LNIT which may account for the clinical improvement are still unclear. OBJECTIVE: To investigate the effects of a successful LNIT-treatment on the allergen-driven T cell response, cytokine secretion and IgE and IgG antibody production. METHODS: Three groups (untreated, subcutaneous immunotherapy- SIT- and LNIT-treated) of grass-sensitive patients suffering from seasonal rhinitic symptoms were ramdomized for the 2-year study. The proliferative response of PBMC to purified Rye-1 allergen and serum levels of grass-specific IgE and IgG were evaluated before treatment and during the 2-year subsequent pollination periods. The proliferative response of allergen-specific short-term T-cell lines, as well as production of allergen-driven cytokine by PBMC, were also assessed. RESULTS: Both SIT and LNIT induced a significant reduction of symptom scores during the pollination season. SIT, but not LNIT, induced a significant change in serum levels of allergen-specific IgE and IgG antibody. By contrast, both SIT and LNIT reduced the increase of the proliferative response of allergen-specific T cells driven by natural allergen exposure and significantly decreased T cell proliferation to low doses of allergen, as shown also by the mitogenic index of allergen-specific T-cell lines. A reduced IL-4 and IFNgamma production by PBMC of LNIT- and SIT-treated patients was also observed in the absence of a clearcut TH2-TH1 switch. CONCLUSIONS: These data suggest that a common mechanism of both LNIT and SIT is the induction of T-cell tolerance, thus providing a rational basis to explain why LNIT may be clinically successful in allergic patients with rhinits.     

Inhibitory effects of methanolic extract from corydalis tuber against types I-IV allergic models

Methanolic extract (CM-ext) from tubers of Corydalis turtschaninovii forma yanhusuo has been screened for activity in experimental models of types I-IV allergy. In type I allergic models, CM-ext at doses of 200, 500 mg/kg, p.o. inhibited 48-h homologous passive cutaneous anaphylaxis (PCA) in rats which is related to IgE, and 4-h heterologous PCA in guinea pigs which is related to IgG. The inhibition of CM-ext on 48-h PCA was also recognized in adrenalectomized rats. CM-ext exhibited the inhibitory effect on formation of IgE antibody in BALB/c mice. In type II allergic model, it was found that CM-ext inhibits reversed cutaneous anaphylaxis (RCA). In type III allergic model, CM-ext showed the inhibitory effect on direct passive arthus reaction (DPAR) in rats. Furthermore, in type IV allergic model, CM-ext had the inhibitory effects on induction phase and effector phase in picryl chloride-induced contact dermatitis (PC-CD). It also showed therapeutic action on PC-CD. These results indicated that CM-ext not only inhibits antibody-mediated allergic reactions but also influences cell-mediated allergic reactions and should be recognized as a potent material for allergic reactions, although the mechanisms and active principles of CM-ext have not yet been completely determined.     

An antagonistic IL-4 mutant prevents type I allergy in the mouse: inhibition of the IL-4/IL-13 receptor system completely abrogates humoral immune response to allergen and development of allergic symptoms in vivo

We have analyzed in vivo effects of the murine IL-4 mutant Q116D/Y119D (QY), which forms unproductive complexes with IL-4Ralpha and is an antagonist for IL-4 and IL-13 in vitro. Treatment of BALB/c mice with QY during immunization with OVA completely inhibited synthesis of OVA-specific IgE and IgG1. BALB/c-derived knockout mice lacking either IL-4 or IL-4Ralpha also did not develop specific IgE or IgG1, but mounted a much stronger IgG2a and IgG2b response than wild-type mice. In contrast, QY treatment of normal BALB/c mice suppressed specific IgG2a, IgG2b, and IgG3 synthesis, which may indicate the development of tolerance toward the allergen. Associated with the lack of IgE synthesis in QY-treated wild-type mice and in IL-4(-/-) mice used as a control was the failure to develop immediate cutaneous hypersensitivity or anaphylactic shock upon rechallenge. Interestingly, QY treatment also inhibited humoral immune responses and allergic reactivity in SJL/J mice, a strain that did not produce IgE, but displayed IgE-independent mast cell degranulation mediated by specific IgG1. We conclude that QY inhibits Ag-specific humoral immune responses and allergic symptoms mediated either by IgE or IgG1. It needs to be clarified how QY abrogates synthesis of IgG2a, IgG2b, and IgG3, but the induction of tolerance toward nonhazardous protein Ags should be advantageous for therapy of atopic disorders and other Th2-dominated diseases.     

CD23 deficient mice develop allergic airway hyperresponsiveness following sensitization with ovalbumin

The low affinity receptor for IgE (CD23) is reported to regulate immune and inflammatory events and as a result, it may have a role in the development of allergic airway inflammation and hyperresponsiveness (AHR). To test this hypothesis CD23-deficient mice were studied following different modes of allergic sensitization. Mice were actively sensitized either intraperitoneally with ovalbumin (OA)/alum or via the airways (10 days exposure to OA aerosol with no adjuvant). Passive sensitization was performed by intravenous injections of OA-specific IgE. Airway responsiveness, serum IgE and IgG levels were assessed together with airway inflammation. Passive sensitization followed by airway challenges resulted in increased OA-specific lgG and IgE in the serum of wild-type mice only, while both the CD23+/+ and CD23-/- groups developed tracheal smooth muscle hyperresponsiveness to electrical field stimulation, indicating that IgE/CD23-mediated immune functions may not be necessary for the development of allergic changes. Active sensitization of both CD23-/- and CD23+/+ mice resulted in increased serum levels of OA-specific IgE and lgG, airway eosinophilia and significant AHR when compared with nonsensitized mice. The genetic deficiency of CD23-/- mice not only failed to prevent but was associated with a significant increase of these responses. These results indicate that CD23 may not be essential for the development of allergen-induced AHR and further, that its presence may have some inhibitory effects on the allergic response.     

Human plasma protein binding of the angiotensin II receptor antagonist losartan potassium (DuP 753/MK 954) and its pharmacologically active metabolite EXP3174

Immunological tolerance can be induced by the oral administration of antigen. We induced oral tolerance rats to experimental allergic conjunctivitis by ovalbumin and investigated the suppression of inflammation. In groups which had started eating antigen both before and after the immunization, the serum anti-ovalbumin IgE level measured by passive cutaneous anaphylaxis reaction was significantly lower than in a group that had not been fed antigen. The intensity of experimental allergic conjunctivitis in the group which had started eating antigen before immunization, was significantly suppressed in regard to the leakage of Evans Blue from conjunctival vessels 30 minutes after the challenge and the neutrophil infiltration 6 hours after. The dye leakage of the group which had started feeding after immunization was also significantly suppressed. There was a positive correlation between the serum IgE level and the leakage of Evans Blue (r = 0.90, p < 0.001). These results suggest that the suppression of antigen-specific IgE antibody production caused by oral tolerance affected the decrease of local inflammation on the conjunctiva.     

Studies on pulmonary and systemic Aspergillus fumigatus-specific IgE and IgG antibodies in horses affected with chronic obstructive pulmonary disease (COPD)

Inhalant exposure to Aspergillus fumigatus (Asp. f.) antigens induces marked inflammatory and immunological alterations in the lungs of horses affected with chronic obstructive pulmonary disease (COPD). In this study we investigated the role of specific allergen(s) present in Asp. f. on systemic and pulmonary IgE and IgG responses in control and COPD-affected horses, using an enzyme-linked immunosorbent assay (ELISA) and immunoblotting techniques. Compared with controls, horses affected with COPD had significantly higher levels of BALF IgE and IgG to somatic Asp. f. antigens as well as to the allergen 1/a (Asp. f. 1/a). Serum levels of IgE and IgG against these antigens did not differ between control and COPD-affected horses. Antigen specific IgE and IgG levels did not correlate between BALF and serum. Scanning of Asp. f. and IgE and IgG blots revealed bands that are recognised by both IgE- and IgG-specific antibodies. Additionally, all horses responded with BALF IgE- and IgG-specific for 93, 35, 31 and 23 kDa allergens, suggesting that these antigens are involved in the induction of airway IgE and IgG responses. These allergens may have the potential to be used as biomarkers for the diagnosis of Asp. f. related exacerbations of equine COPD.     

Inhibitory mechanisms of beta-adrenoceptor agonists for immunoglobulin E-mediated experimental allergic reactions in rats

Inhibitory mechanisms of isoproterenol and clenbuterol for immunoglobulin E (IgE)-mediated experimental allergic reactions in rats were studied. IgE-mediated passive cutaneous anaphylaxis, histamine-induced cutaneous reaction and serotonin-induced cutaneous reaction were evoked at the same time in the same rats. Isoproterenol administered intravenously immediately before challenge inhibited all these reactions significantly. Clenbuterol administered intravenously 0-3 h before challenge also significantly inhibited the three cutaneous reactions. The inhibition was maximum when the drug was given 1 h before challenge. Passive cutaneous anaphylaxis was always inhibited more potently than histamine-induced cutaneous reaction and serotonin-induced cutaneous reaction by these beta-adrenoceptor agonists. Passive peritoneal anaphylaxis was caused by injecting an antigen intravenously. Isoproterenol administered intravenously immediately before challenge inhibited the reaction significantly. Clenbuterol administered intravenously 0-3 h before challenge also significantly inhibited passive peritoneal anaphylaxis, maximally so when given 1 h before challenge. In vitro IgE-dependent histamine release from sensitized peritoneal mast cells or mesenteric mast cells was not affected by isoproterenol and clenbuterol. Mouse monoclonal IgE, a foreign protein, administered intravenously decreased rapidly in the circulation. About 50% of the mouse IgE given disappeared in 20 min. The decrease of mouse IgE was partly but significantly inhibited by the beta-adrenoceptor agonists, and the inhibition was abolished by simultaneous treatment with propranolol. These results indicate that direct inhibition of mast cell activation does not contribute to the potent inhibition of in vivo allergic reactions in rats by beta-adrenoceptor agonists, and that inhibition of the allergic cutaneous reaction is partially explained by the inhibition of vascular permeability increases caused by mast cell mediators. Penetration of intravenously administered antigen from blood vessels to peripheral tissues to cause mast cell activation might be inhibited by beta-adrenoceptor agonists, and this could play some role in inhibiting intravenous antigen-induced allergic reactions in rats. Clenbuterol exhibited its maximum action with some latency in vivo, suggesting that some time-requiring process may be involved in the manifestation of its action.     

Glucocorticoids inhibit human antigen-specific and enhance total IgE and IgG4 production due to differential effects on T and B cells in vitro

Although anti-inflammatory properties of glucocorticoids (GC) are well documented, their activity in allergic diseases is still controversial. Recently, it has been reported that GC can increase, both in vivo and in vitro, the polyclonal production of total IgE. In this study we investigated the effects of GC on the antigen (Ag)-specific IgE response in a human in vitro system with peripheral blood mononuclear cells or B cells of bee venom-sensitized individuals that allows the production of bee venom phospholipase A2 (PLA)-specific IgE and IgG4 antibodies (Ab). PLA-specific Ab were induced by simultaneously activating T cells and B cells specifically with allergen and polyclonally with anti-CD2 and soluble CD40 ligand (sCD40L) in the presence of interleukin (IL)-4. Indeed, dexamethasone and prednisolone enhanced the formation of total IgE and IgG4 in PBMC, while the production of PLA-specific IgE and IgG4 Ab was selectively inhibited in a dose-dependent manner. The suppressive effect of GC was mediated during Ag-specific stimulation and T cell-B cell interaction. This was due to GC suppressing specific T cell proliferation and cytokine production, whereas neither allergen-specific nor total IgE and IgG4 production by sCD40L/IL-4-stimulated pure B cells was affected. In contrast to GC, cyclosporine A inhibited both total and PLA-specific IgE and IgG4 secretion in peripheral blood mononuclear cells and B cell cultures. Further experiments showed that increase in nonspecific total isotype response resulted from inhibition of IL-4 uptake by cells other than B cells and sufficient availability of IL-4 to B cells for isotype switch and synthesis. Furthermore, demonstration of opposite regulatory effects of GC on specific and total isotype formation in vitro, including the inhibition of allergy-relevant Ag-specific IgE response, may contribute to a better understanding of apparently controversial observations, and explain why most allergic patients benefit from GC therapy.     

Differential regulation of human T cell cytokine patterns and IgE and IgG4 responses by conformational antigen variants

Bee venom phospholipase A2 (PLA) represents the major allergen and antigen in allergic and non-allergic individuals sensitized to bee sting. We have studied specific activation of peripheral T cells by different structural and conformational variants of PLA and secretion of cytokines regulating IgE and IgG4 antibody (Ab) formation. PLA molecules expressing the correctly folded tertiary structure, which show high affinity to membrane phospholipids and were recognized by Ab from bee sting allergic patients, induced high IL-4, IL-5 and IL-13 production in peripheral blood mononuclear cell cultures. In contrast, non-refolded recombinant PLA (rPLA) and reduced and alkylated native PLA (nPLA) induced more IFN-gamma and IL-2 and higher proliferative responses. Differences in proliferation and cytokine patterns among correctly folded and non-refolded PLA resulted from conformation-dependent involvement of different antigen-presenting cell (APC) types. Antigen (Ag)-presenting B cells recognized PLA only in its natural conformation, stimulated Th2 type cytokines and induced IgE Ab. Non-refolded PLA was recognized, processed and presented exclusively by monocytes and induced a Th1 dominant cytokine profile leading to IgG4 production by B cells. The possibility that production of particular cytokine patterns and Ig isotype was influenced by the enzymatic activity of PLA was excluded by using enzymatically inactive H34Q point-mutated, refolded rPLA. These findings demonstrate the decisive role of specific Ag recognition by different APC, depending on structural features, membrane phospholipid binding property and the existence of conformational B cell epitopes, in the differential regulation of memory IgE and IgG4 Ab. Furthermore, they show that a change from IgE-mediated allergy to normal immunity against a major allergen can be induced by rPLA variants that are not recognized by specific Ab and B cells but still carry the T cell epitopes. These features may enable new applications for safer immunotherapy.     

Effect of reference database on frequency estimates of polymerase chain reaction (PCR)-based DNA profiles

1. To assess the contribution of an aqueous extract of Ulmi radicis cortex (AEURC) in systemic anaphylaxis, compound 48/80 was used as a fatal anaphylaxis inducer in rats. 2. AEURC completely inhibited anaphylactic shock with a dose of 1.0 g/kg body weight (BW) 1 hr before injection of compound 48/80. 3. AEURC significantly inhibited serum histamine levels induced by compound 48/80. 4. AEURC (1.0 g/kg BW) also inhibited by 79.1% passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. 5. AEURC dose dependently inhibited the histamine release from the rat peritoneal mast cells (RPMCs) by compound 48/80. Moreover, AEURC had a significant inhibitory effect on anti-DNP IgE-induced histamine release and tumor necrosis factor-alpha production from RPMC. 6. The level of cAMP in RPMC, when AEURC was added, significantly increased compared with that of a normal control. 7. These results indicate that AEURC may possess strong antianaphylactic action.     

Inhibition of immediate type allergic reactions by the aqueous extract of Kum-Hwang-San

We studied the effect of aqueous extract of Kum-Hwang-San (KHS) on mast cell-mediated immediate type allergic reactions. KHS (1-100 microg/site) inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48/80 (200 microg/site) in mice by both topical and intradermal application. KHS (0.1-100 microg/site) inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by both topical and intradermal application. KHS also inhibited concentration-dependently the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 and anti-DNP IgE. Moreover, KHS had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) secretion from RPMC. These results indicate that KHS inhibits immediate type allergic reactions by inhibition of histamine release and TNF-alpha secretion from mast cells in vivo and in vitro.     

Relation between bronchial reactivity to antigen in vivo and serum IgE and IgG2a antibody levels in rats

Sprague Dawley rats were immunized with graded doses of ovalbumin (OA) together with alum. The capacity of the animals to produce a bronchial anaphylactic response to intravenous antigen challenge was related to serum OA-IgE and OA-IgG2a antibody levels estimated by radioimmunoassay. A significant correlation between bronchial anaphylactic response capacity and OA-IgE antibody levels was found under a few, but not all, of several carefully chosen experimental conditions. No correlation was demonstrable between the in vivo reactivity of the animals and their serum levels of OA-specific IgG2a antibodies.     

Suppression of the benzylpenicilloyl- (BPO) specific IgE formation with isologous anti-idiotypic antibodies in BALB/c mice

In vivo effects of actively produced or passively administered isologous anti-idiotypic antisera (aId) on the benzylpenicilloyl- (BPO) specific IgE and IgG formation in BALB/c mice have been studied. Isologous anti-BPO aId were raised in BALB/c mice by immunization with purified anti-BPO antibodies isolated from ascites induced with BPO-bovine gamma-globulin in the same mouse strain. Mice producing isologous anti-BPO aId exhibited long-term suppression of BPO-specific IgE and IgG antibody responses induced by BPO-ovalbumin (BPO-OVA) in aluminum hydroxide. Simultaneously, they produced increased amounts of anti-BPO aId after each challenge with the BPO-OVA antigens. Passive administration of isologous anti-BPO aId into syngeneic mice previously sensitized with BPO-OVA caused depression of BPO-specific IgE antibody levels for 2 to 3 weeks. When anti-BPO IgE had again reached its previous level, passively administered aId had decreased to the level of untreated mice. Passive administration of anti-BPO aId also depressed the primary anti-BPO IgE formation for 2 to 3 weeks. In all these experiments the IgE antibody formation against the carrier proteins used for BPO-antigens was not affected. These results show that IgE and IgG antibodies share major idiotypic determinants and that IgE production is accessible to regulation by aId.