Airway effects of inhaled quaternary ammonium compounds in mice

Quaternary ammonium compounds (QAC) constitute a family of widely used chemical substances. The QAC benzalkonium chloride (BAC) has caused bronchoconstriction in human beings by poorly understood mechanisms and lung damage at high concentration as shown in a single rat study. This study evaluates acute airway effects in mice after inhalation of aerosols of the QACs, BAC, hexadecyl trimethyl ammonium bromide (HTA), cetyl pyridinium chloride (CPC) and dimethyl dioctadecyl ammonium bromide (DDA). The QACs gave rise to concentration-dependent decreases in the tidal volume (VT) and a concomitant increase in respiratory rate indicating pulmonary irritation. The potencies of the QAC to induce these effects were in the order: BAC > HTA = CPC > DDA. Furthermore, inhalation of BAC and CPC aerosols gave rise to pulmonary inflammation as apparent from bronchoalveolar lavage. Stimulation of nasal trigeminal nerve endings by QAC, which may serve as a warning signal, was absent.     

Fine particles of widely different composition have an adjuvant effect on the production of allergen-specific antibodies

Diesel exhaust particles (DEP) are reported to increase the specific IgE response to allergens, and results from our laboratory suggest that the particle core of DEP contribute to this adjuvant activity. The purpose of the present study was to explore further the adjuvant effect of particles per se, that is particles by themselves. NIH/Ola mice were given two intraperitoneal injections with ovalbumin (OVA; 10 microg) alone or OVA in combination with PSP, polytetrafluoroethylene (teflon), titanium dioxide (TiO(2)) or amorphous silica particles (2.8x10(10)-2.8x10(12)). Blood samples were drawn 7 days after the last injection, and serum levels of allergen-specific and total IgE and IgG2a were measured. All types of particles gave increased levels of allergen-specific IgE and IgG2a. Similar results were obtained after intranasal or intratracheal instillation with OVA plus PSP or silica. Our results indicate that fine particles of widely different composition may have an adjuvant effect on the production of allergen-specific antibodies.     

Airway inflammation and adjuvant effect after repeated airborne exposures to di-(2-ethylhexyl)phthalate and ovalbumin in BALB/c mice

BACKGROUND: Epidemiological studies have suggested an association between exposure to phthalate plasticizers, including di-(2-ethylhexyl)phthalate (DEHP), and increased prevalence of asthma, rhinitis or wheezing. Furthermore, studies in mice have demonstrated an adjuvant effect from DEHP after parenteral administration with the model allergen ovalbumin (OVA). OBJECTIVE: Exposures to DEHP were investigated for adjuvant effects and airway inflammation in a mouse inhalation model. METHODS: BALB/cJ mice were exposed to aerosols of 0.022-13 mg/m(3) DEHP and 0.14 mg/m(3) OVA 5 days/week for 2 weeks and thereafter weekly for 12 weeks. Mice exposed to OVA alone or OVA+Al(OH)(3) served as control groups. Finally, all groups were exposed to a nebulized 1% OVA solution on three consecutive days. Serum, bronchoalveolar lavage (BAL) fluid, and draining lymph nodes were collected 24h later. RESULTS: In the OVA+Al(OH)(3) group, significantly increased levels of OVA-specific IgE and IgG1 in serum as well as of eosinophils in BAL fluid were observed. DEHP affected OVA-specific IgG1 production in a concentration-dependent manner, whereas little effect was seen on IgE and IgG2a. Dose-dependent increases in inflammatory cells were observed in BAL fluids, leading to significantly higher lymphocyte, neutrophil and eosinophil numbers in the OVA+13 mg/m(3) DEHP group. Ex vivo cytokine secretion by cultures of draining lymph nodes suggested that DEHP has a mixed Th1/Th2 cytokine profile. CONCLUSION: Airborne DEHP is able to increase serum IgG1 and lung inflammatory cell levels, but only at very high concentrations. Realistic DEHP levels do not have an adjuvant effect or induce allergic lung inflammation in the present mouse model.     

Development of sensitisation or tolerance following repeated OVA inhalation in BALB/cJ mice. Dose-dependency and modulation by the Al(OH)3 adjuvant

Anthropogenically induced exposures may, due to their adjuvant effect, promote development of sensitisation to commonly occurring aeroallergens. No generally accepted model exists for determination of adjuvant effect of airborne substances. Therefore, BALB/cJ mice were exposed for 10 consecutive days with ovalbumin (OVA) solution, 25 mg/l-10 g/l (0.0025-1%) for 20 min/day, with and without the Al(OH)(3) adjuvant (0.5%). Four days after the last aerosol exposure, no OVA specific IgE and only low IgG1 were produced. Subsequent parenteral OVA administration showed that the 10 g/l solution induced full tolerance of the IgE response, whereas only partial tolerance was apparent with 25 mg/l OVA. The Al(OH)(3) adjuvant counteracted development of tolerance that was fully prevented at the 25 mg/l OVA concentration. Development of IgG1 was increased in a concentration-dependent manner with 500 mg/l-10 g/l OVA. No increase occurred at the 25 mg/l level, but addition of Al(OH)(3) increased IgG1 production to the same level as the higher OVA concentrations. Concentrations from 1.25 mg/l to 10 g/l OVA were studied with ten exposures followed by once-weekly aerosol exposure for uptil 6 weeks. In the range from 1.25 mg/l to 10 g/l, IgE production was time- and concentration-dependent. Both the IgE and IgG1 production were markedly promoted by Al(OH)(3). However, with aerosol exposures, the IgE antibody productions were not sufficient to increase the level of inflammatory cells in broncho-alveolar lavage fluid. Overall, this study showed that airborne Al(OH)(3) was able to counteract tolerance and increase specific IgE and IgG1 production.     

IgE adjuvant effect caused by particles - immediate and delayed effects

Diesel exhaust particles are reported to increase the specific IgE response to ovalbumin (OVA) and pollen. Evidence has been provided that the particle core contributes to this adjuvant activity. The purpose of our study was to investigate the effect of well-defined simple particles, polystyrene particles (PSP), on the production of allergen-specific IgE in a mouse model. The IgE adjuvant effect of PSP was investigated in experiments using intranasal (i.n.) instillation, intratracheal (i.t.) instillation or intraperitoneal (i.p.) injection. Delayed and cumulative adjuvant effects were investigated by giving mice i.p. injections with PSP 1-3 days, or on 4 consecutive days before OVA, respectively. The levels of allergen-specific and total IgE were measured. Irrespectively of immunisation route and protocol, OVA in combination with PSP elicited increased levels of both allergen-specific and total IgE when compared with OVA alone. Therefore, in the experimental model, particles were found to augment the specific IgE response to an allergen even when the allergen was introduced several days after the particles. These findings imply that individuals exposed to particulate air pollution at one point of time may develop an increased reaction towards allergens inhaled later that day or even several days after the particle exposure.     

Nano Titanium Dioxide Particles Promote Allergic Sensitization and Lung Inflammation in Mice

Abstract: The purpose of this study was to investigate whether photocatalytic TiO₂ nanoparticles have adjuvant effect, when administered in combination with ovalbumin (OVA) in mice. Mice were immunized via intraperitoneal injections of OVA, OVA + TiO₂ or OVA + Al(OH)₃ and challenged with aerosols of OVA. At the end of the study, serum was analysed for content of OVA‐specific IgE, IgG1 and IgG2a antibodies, and the bronchoalveolar lavage fluid (BALF) was analysed for content of inflammatory cells and levels of interleukin (IL)‐4, IL‐5, IL‐10 and interferon‐γ. The TiO₂ particles promoted a Th2 dominant immune response with high levels of OVA‐specific IgE and IgG1 in serum and influx of eosinophils, neutrophils and lymphocytes in BALF. The TiO₂ particles induced a significantly higher level of OVA‐specific IgE than the standard adjuvant Al(OH)₃. However, the two substances were comparable regarding the level of eosinophilic inflammation and interleukins present in BALF.     

Adjuvant effects of inhaled mono-2-ethylhexyl phthalate in BALB/cJ mice

Phthalates, including di(2-ethylhexyl) phthalate (DEHP), are widely used and have been linked with the development of wheezing and asthma. The main metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP), was investigated for adjuvant effects in a mouse inhalation model. BALB/cJ mice were exposed to aerosols of 0.03 or 0.4 mg/m(3) MEHP 5 days/week for 2 weeks and thereafter weekly for 12 weeks together with a low dose of ovalbumin (OVA) as a model allergen. Mice exposed to OVA alone or OVA+Al(OH)(3) served as negative and positive controls, respectively. Finally, all groups were exposed to a nebulized 1% OVA solution on 3 consecutive days to investigate the development of an inflammatory response. Serum, bronchoalveolar lavage (BAL) fluid, and draining lymph nodes were collected 24h later. In the OVA+Al(OH)(3) group, significantly increased levels of OVA-specific IgE and IgG1 in serum as well as of eosinophils in BAL fluid were observed. OVA-specific IgG1 production in both MEHP groups was significantly increased. OVA-specific IgE and IgG2a were not increased significantly. A dose-dependent increase in inflammatory cells was observed in BAL fluid, leading to significantly higher lymphocyte and eosinophil numbers in the OVA+0.4 mg/m(3) MEHP group. Ex vivo cytokine secretion by cultures of draining lymph nodes suggested a T(H)2 profile of MEHP. In conclusion, MEHP acted as a T(H)2 adjuvant after inhalation. However, it is suggested that the inflammation in the MEHP groups was primarily mediated by an IgG1-dependent mechanism. To address implications for humans, a margin-of-exposure was estimated based on the lack of significant effects on IgE production and inflammation after exposures to 0.03 mg/m(3) MEHP observed in the present study and estimated human exposure levels.     

Effect of diesel exhaust particles and their components on the allergen-specific IgE and IgG1 response in mice

Increased antigen-specific IgE expression is a hallmark of the allergic response in mice. IgG1 may also be involved. Co-injection of mice with diesel exhaust particles (DEP) and ovalbumin three times over a 2 week period lead to a rapid and marked elevation of ovalbumin-specific IgE, IgG1 and also IgG2a, compared with ovalbumin alone. When DEP were injected 1 day before or after ovalbumin on each occasion, their adjuvant effect was considerably muted, suggesting that the adjuvant effect of DEP is short-lived, or that a physical interaction between ovalbumin and DEP is required. DEP were extracted with methylene chloride. Both the resulting core carbon particles and the organic extract enhanced ovalbumin specific IgE and IgG1 levels. Thus the adjuvant effect of DEP in this model is due both to the physical and the chemical attributes of the particles. The tricyclic hydrocarbons phenanthene (the most prevalent polycyclic aromatic hydrocarbon in DEP) and anthracene were both capable of enhancing antigen-specific IgE and IgG1 production. The phenolic antioxidant, butylated hydroxyanisole, which can affect gene expression via the antioxidant responsive element (ARE), had a lesser effect. Two agonists for the aryl hydrocarbon receptor, 3-methychloranthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin, either were without effect or suppressed the response, suggesting that DEP adjuvancy may not be mediated by this receptor.     

Allergy adjuvant effect of particles from wood smoke and road traffic

There is growing evidence that in addition to augmenting the severity of asthma and allergic diseases, particulate air pollution also increases the incidence of allergy and asthma. We studied the adjuvant effect of particles from wood smoke and road traffic on the immune response to the allergen ovalbumin (OVA). OVA with and without particles was injected into one hind footpad of Balb/cA mice. All particles together with OVA significantly increased the level of OVA-specific immunoglobulin E (IgE) in serum, compared to groups given OVA or particles alone. Reference diesel exhaust particles (DEP) with OVA induced the highest levels of IgE, whereas no clear difference was observed between particles from road traffic and wood smoke. Road traffic particles collected in the autumn induced higher IgE values with OVA than corresponding particles collected during the winter season when studded tires are used, suggesting that studded tire-generated road pavement particles have less allergy adjuvant activity than exhaust particles. Compared to OVA or particles alone, all particles with OVA increased popliteal lymph node cell numbers, cell proliferation, ex vivo secretion of IL-4 and IL-10 after ConA stimulation, and the expression of several cell surface molecules (CD19, MHC class II, CD86 and CD23). Wood smoke particles with OVA induced somewhat higher cellular responses than road traffic particles, but less than DEP with OVA which seemed to be the most potent particle in inducing cellular as well as antibody responses. Thus, wood smoke particles had about the same capacity to enhance allergic sensitization as road traffic particles, but less than diesel exhaust particles.     

The fungal biopesticide Metarhizium anisopliae has an adjuvant effect on the allergic response to ovalbumin in mice

The parasitic fungus, Metarhizium anisopliae, is non-pathogenic to humans and licensed for indoor control of cockroach infestation. An important reason for the elimination of this vermin is that sensitisation to cockroaches is associated with asthma. Previously M. anisopliae has been shown to cause allergic- and asthma-like responses in mice and in the present study we have examined the adjuvant activity of M. anisopliae on the allergic response to the model allergen ovalbumin (OVA) in a mouse model. Levels of OVA-specific IgE, IgG1 and IgG2a in serum were measured and the weight and cell number of the excised popliteal lymph node were determined. Mice primed with mycelium+OVA and boosted with OVA had increased anti-OVA IgE and IgG1 levels compared with mice primed with OVA alone or mycelium. Priming with M. anisopliae (as mycelium or MACA) increased weight or cell number of the excised PLNs. These results suggest that M. anisopliae has the ability to increase an allergic response to an allergen and consequently, may worsen allergy in susceptible individuals.     

Haemolytic activities and adjuvant effect of Anemone raddeana saponins (ARS) on the immune responses to ovalbumin in mice

In this study, saponins (ARS) extracted from the rhizoma of Anemone raddeana were evaluated for their haemolytic activities and its potential ability as adjuvant on the cellular and humoral immune responses of ICR mice against ovalbumin. The haemolytic activity of ARS was determined using 0.5% rabbit red blood cell. ARS showed a slight haemolytic effect, with its haemolytic percents being 16.50 and 3.56% at the concentrations of 500 and 250 microg/ml, respectively. ICR mice were immunized subcutaneously with OVA 100 microg alone or with OVA 100 mug dissolved in saline containing Alum (200 microg), QuilA (10 and 20 microg) or ARS (50, 100 or 200 microg) on Days 1 and 15. Two weeks later (Day 28), concanavalin A (Con A)-, lipopolysaccharide (LPS)- and OVA-stimulated splenocyte proliferation and OVA-specific antibodies in serum were measured. ARS significantly enhanced the Con A-, LPS-, and OVA-induced splenocyte proliferation in the OVA-immunized mice especially at a dose of 100 microg (P<0.01 or P<0.05). The OVA-specific IgG, IgG1 and IgG2b antibody levels in serum were also significantly enhanced by ARS compared with OVA control group (P<0.01 or P<0.05). Moreover, no significant differences (P>0.05) were observed between enhancing effect of ARS and QuilA on the OVA-specific IgG2b antibody responses to OVA in mice. The results suggest that ARS showed a slight haemolytic effect and enhanced significantly a specific antibody and cellular response against OVA in mice.     

Induction of IgE antibody responses by protein allergens: inter-laboratory comparisons.

There is a growing interest in the development of methods for the evaluation of the allergenic potential of novel proteins. One approach is the measurement of specific IgE antibody production stimulated by systemic (intraperitoneal; i.p.) exposure of BALB/c strain mice. In the current investigations, inter-laboratory comparisons have been performed of IgE antibody production induced in mice by food proteins of differing sensitizing potential. Female BALB/c strain mice (n=5) were exposed to 0.1% peanut agglutinin, an allergenic constituent of peanuts, to 2% ovalbumin (OVA), a major allergenic constituent of hens' egg, or to a protein considered to lack significant allergenicity, potato agglutinin (5%). Specific IgE antibody was measured by homologous passive cutaneous anaphylaxis assay and IgG and IgG1 antibody production was analysed by enzyme-linked immunosorbent assay (ELISA). Two independent experiments were conducted in each laboratory, but with all serological analyses conducted in one of the laboratories. Each of the proteins induced vigorous IgG and IgG1 antibody responses, with no statistically significant differences in titres recorded between laboratories. Furthermore, OVA and potato agglutinin induced responses of equivalent immunogenicity with respect to both IgG and IgG1 antibody titres. Administration of peanut agglutinin and OVA each stimulated marked IgE antibody responses in every experiment. In the two laboratories, titres ranged from 1:32 and 1:64 for peanut agglutinin, and from 1:8 and 1:32 for OVA. In contrast, exposure to potato agglutinin failed to induce vigorous IgE production, with no detectable IgE (negative with neat serum), or titres of 1 (positive with neat serum only) recorded. These data demonstrate that the induction of IgE antibody by food proteins of differing allergenic potential is a relatively robust phenomenon and transferable between laboratories. Furthermore, these results provide additional evidence that the measurement of antibody (IgE) responses in BALB/c mice may allow discrimination between allergens and those materials that apparently lack allergenicity.     

Immunological adjuvant effect of Boswellia serrata (BOS 2000) on specific antibody and cellular response to ovalbumin in mice

In this study, the biopolymeric fraction BOS 2000 from Boswellia serrata was evaluated for its potential ability as adjuvants on the immune responses to ovalbumin (OVA) in mice. Balb/c mice were immunized subcutaneously with OVA 100 μg alone or with OVA 100 μg dissolved in saline containing alum (200 μg) or BOS 2000 (10, 20, 40 and 80 μg) on Days 1 and 15. Two weeks later, OVA specific antibodies in serum; concanavalin A (Con A), OVA stimulated splenocyte proliferation, CD4/CD8/CD80/CD86 analysis in spleen cells and its estimation of cytokines (IL-2 and IFN gamma) from cell culture supernatant were measured. OVA specific IgG, IgG1 and IgG2a antibody levels in serum were significantly enhanced by BOS 2000 (80 μg) compared with OVA control group. Moreover, the adjuvant effect of BOS 2000 (80 μg) on the OVA-specific IgG, IgG1, and IgG2a antibody responses to OVA in mice were more significant than those of alum. BOS 2000 significantly enhanced the Con A and OVA induced splenocyte proliferation in the OVA immunized mice especially at a dose of 80 μg (p<0.001). However, no significant differences were observed among the OVA group and OVA/alum group. At a dose of 80 μg (p<0.001), there was a significant increase in the CD4/CD8 and CD80/CD86 analysis in spleen cells and cytokine (IL-2 and IFN-gamma) profile in the spleen cell culture supernatant was observed. In conclusion, BOS 2000 seems to be a promising balanced Th1 and Th2 directing immunological adjuvants which can enhance the immunogenicity of vaccine.     

The adjuvant effect of di-(2-ethylhexyl) phthalate is mediated through a PPARalpha-independent mechanism

Previous studies in BALB/c mice revealed an adjuvant effect of di-(2-ethylhexyl) phthalate (DEHP) to simultaneously administered ovalbumin. DEHP is the most commonly used phthalate plasticizer. In vivo formed metabolites of DEHP are peroxisome-proliferator-activated receptor (PPAR) ligands, a group of chemicals that may have immunomodulatory properties. To study whether the PPARalpha receptor was involved in the adjuvant effect of DEHP, PPARalpha-deficient 129/Sv mice were exposed intraperitoneally to a mixture of OVA and DEHP, and the OVA-specific IgE, IgG1 and IgG2a responses were compared to the corresponding responses in the wild-type strain. The study showed that the adjuvant mechanism of DEHP is mediated through a PPARalpha-independent mechanism. Compared to mice only given OVA, DEHP induced highly increased levels of OVA-specific IgG1 and IgG2a, both in the wild-type and in the PPARalpha knock-out strains, indicating that DEHP is a mixed Th1/Th2 adjuvant.     

Adjuvant and immuno-suppressive effect of six monophthalates in a subcutaneous injection model with BALB/c mice.

The prevalence of allergic airway diseases is rapidly increasing in Western Europe and North America. This increase in disease prevalence may be associated with environmental pollutants. The present study investigated the adjuvant and immuno-suppressive effect of a series of monophthalates which are considered to be important metabolites of commonly used phthalate plasticizers. The effects were studied in a screening model. Ovalbumin (OA), used as the model antigen, was injected subcutaneously in the neck region of BALB/cJ mice with or without one of the test substances, mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBnP), mono-n-octyl phthalate (MnOP), mono-2-ethylhexyl phthalate (MEHP), mono-iso-nonyl phthalate (MiNP) or mono-iso-decyl phthalate (MiDP). The levels of OA-specific IgE, IgG1 and IgG2a in sera were measured by ELISA. Immuno-suppressive effect, defined as a statistically significant reduction in IgE or IgG1 antibody production, was observed with MEHP (1000 microg/ml, IgE and IgG1), MnOP (1000 microg/ml, IgE and IgG1), MiNP (1000 microg/ml, IgE and 10 microg/ml, IgG1) and MiDP (100 microg/ml, IgE and IgG1). Adjuvant effect, defined as a statistically significant increase in IgE or IgG1 antibody level, occurred with MEHP (10 microg/ml, IgE), MnOP (100 microg/ml, and 10 microg/ml, IgG1) and MiNP (100 microg/ml, IgE). No statistically significant immune modulating effect was seen with MBnP and MnBP.     

The IgE adjuvant effect of particles: characterisation of the primary cellular response in the draining lymph node

Diesel exhaust particles, and polystyrene particles (PSP) as a model for the insoluble particle core, have an adjuvant effect on allergen-specific IgE production in mice. We therefore examined the primary immune response in the draining popliteal lymph node (PLN) to the allergen ovalbumin (OVA) injected together with polystyrene particles into the footpad of BALB/cA mice. Similar numbers of particle-containing cells were observed in the draining lymph node on day 1 after injection of PSP alone or OVA + PSP, the numbers increasing continuously until day 21. The total lymph node cell numbers increased three to four times in the OVA + PSP group compared to both OVA and PSP groups, peaking on day 5. The increase in B cell numbers was twice the increase in T cell numbers. On day 5, OVA + PSP increased the expression of most surface markers measured (MHC class II, CD86, CD23, CD69) compared to OVA and PSP. Further, the ex vivo production of IL-4 and IL-10 by PLN cells from OVA + PSP-injected animals was increased. In conclusion, whereas PSP alone did not influence any of the immunologic markers studied, the adjuvant effect of PSP on the IgE antibody response to OVA was associated with an early increased primary cellular response in the draining lymph node.     

Divergent antibody isotype responses induced in mice by systemic exposure to proteins: a comparison of ovalbumin with bovine serum albumin.

Whereas many foreign proteins are immunogenic, only a proportion is associated commonly with allergy, having the potential to induce the quality of immune response necessary for IgE antibody production and the development of immediate type hypersensitivity reactions in the gastrointestinal and/or respiratory tracts. In the context of toxicological evaluations there is a need to identify those properties that confer on proteins the ability to provoke allergic reactions. The characteristics of antibody responses induced in BALB/c strain mice following administration of ovalbumin (OVA), a significant human allergen, have been compared with those provoked by bovine serum albumin (BSA), a protein considered to have more limited allergenic potential. Intranasal or intraperitoneal (ip) administration of BSA or OVA elicited vigorous IgG and IgG1 antibody responses. Differential IgE antibody production was observed, however, with OVA stimulating relatively high IgE antibody titres at all doses tested whereas no or low titre IgE antibody was detected following exposure to BSA. Furthermore, a differential capacity for IgG2a antibody responses was observed, with only BSA provoking high titres of this IgG subclass. The relative quality of induced responses was equivalent following administration of these proteins via mucosal (in) tissue or via a non-mucosal (ip) route of exposure. IgG2a antibody production is promoted by the type 1 cytokine interferon gamma (IFN-gamma), whereas IFN-gamma and the type 2 cell product interleukin 4 exert reciprocal antagonistic effects on IgE antibody responses. Although cytokine expression patterns were not analysed in this series of experiments, the differential IgE and IgG subclass antibody responses induced by BSA and OVA are consistent with the preferential activation of T helper (Th) 1- and Th2-type cells, respectively. These data indicate that proteins can provoke in mice characteristic antibody (IgE and IgG) isotype profiles suggestive of discrete T lymphocyte responses and that such differences may be associated with variable allergenic activity.     

三七皂苷的溶血性及免疫佐剂作用

目的:评价三七皂苷的溶血性及免疫佐剂作用。方法:以分光光度法测定三七皂苷对红细胞的溶血百分率;以卵白蛋白(OVA) 100μg、OVA 100μg加氢氧化铝2mg及OVA 100μg加不同剂量三七皂苷(50、100、200μg)分别免疫ICR小鼠,二次免疫(间隔14天)后,用MTT法检测Con A、PWM和PHA诱导脾淋巴细胞增殖反应,ELISA检测血清中的抗OVA抗体效价。结果:三七皂苷浓度为500和250mg/L时红细胞的溶血百分率分别为11.6％和3.6％;OVA加三七皂苷100μg免疫组小鼠Con A、PWM和PHA诱导的脾淋巴细胞增殖反应显著高于OVA对照组(P<0.01);OVA加三七皂苷(50、100、200μg)免疫细小鼠血清中抗OVA抗体效价高于OVA对照组(P<0.01)。结论:三七皂苷具有免疫佐剂活性及较低的溶血性。     

Exposure of brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation.

Exposure to diesel exhaust particles (DEP) during the sensitization process has been shown to increase antigen-specific IgE production and aggravate allergic airway inflammation in human and animal models. In this study, we evaluated the effect of short-term DEP exposure on ovalbumin (OVA)-mediated responses using a post-sensitization model. Brown Norway rats were first exposed to filtered air or DEP (20.6 +/- 2.7 mg/m3) for 4 h/day for five consecutive days. One day after the final air or DEP exposure (day 1), rats were sensitized with aerosolized OVA (40.5 +/- 6.3 mg/m3), and then again on days 8 and 15, challenged with OVA on day 29, and sacrificed on days 9 or 30, 24 h after the second OVA exposure or the final OVA challenge, respectively. Control animals received aerosolized saline instead of OVA. DEP were shown to elicit an adjuvant effect on the production of antigen-specific IgE and IgG on day 30. At both time points, no significant airway inflammatory responses and lung injury were found for DEP exposure alone. However, the OVA-induced inflammatory cell infiltration, acellular lactate dehydrogenase activity and albumin content in bronchoalveolar lavage (BAL) fluid, and numbers of T cells and their CD4+ and CD8+ subsets in lung-draining lymph nodes were markedly reduced by DEP on day 30 compared with the air-plus-OVA exposure group. The OVA-induced nitric oxide (NO) in the BAL fluid and production of NO, interleukin (IL)-10, and IL-12 by alveolar macrophages (AM) were also significantly lowered by DEP on day 30 as well as day 9. DEP or OVA alone decreased intracellular glutathione (GSH) in AM and lymphocytes on days 9 and 30. The combined DEP and OVA exposure resulted in further depletion of GSH in both cell types. These results show that short-term DEP exposure prior to sensitization had a delayed effect on enhancement of the sensitization in terms of allergen-specific IgE and IgG production, but caused an attenuation of the allergen-induced airway inflammatory responses.     

Study of adjuvant effect of model surfactants from the groups of alkyl sulfates, alkylbenzene sulfonates, alcohol ethoxylates and soaps.

The sodium salts of representatives of anionic surfactants, dodecylbenzene sulfonate (SDBS), dodecyl sulfate (SDS) and coconut oil fatty acids, and a nonionic surfactant, dodecyl alcohol ethoxylate, were studied for adjuvant effect on the production of specific IgE antibodies in mice. The surfactants were injected subcutaneously (sc) in concentrations of 1000, 100, 10 or 1 mg/l, respectively, together with 1 microg of ovalbumin (OVA). In addition, groups of mice received OVA in saline (control group) or in Al(OH)(3) (positive adjuvant control group). After the primary immunization the mice were boosted up to three times with OVA (0.1 microg sc) in saline. OVA-specific IgE antibodies were determined by the heterologous mouse rat passive cutaneous anaphylaxis test. The results were confirmed by a specific ELISA method. After the first booster, the Al(OH)(3) group and the 10 mg/l SDS group showed a statistically significant increase in OVA specific IgE levels. After two boosters, a statistically significant suppression in OVA-specific IgE production occurred with SDS (1000 mg/l), SDBS (1000 and 100 mg/l), coconut soap (1000 mg/l) and the alcohol ethoxylate (10 mg/l). This study suggests that a limited number of surfactants possess an adjuvant effect whereas all surfactants at certain levels can suppress specific IgE production.