Eosinophilia In Guinea Pigs Research Articles

Evaluation of Anti-Asthmatic and <i>In Vitro</i> Anti-Oxidant Potential of <i>Tragia involucrata</i> Linn

The objective is to evaluate the in vivo anti-asthmatic and in vitro antioxidant potential of Hydroalcoholic Leaf Extract of Tragia involucrata (HAETI) on experimental animals. In vivo anti-asthmatic activity of HAETI was evaluated by Arachidonic acid-induced Leucocytosis and Eosinophilia in guinea pigs, Arachidonic acid-induced mast cell degranulation in guinea pigs, and Mast cell Degranulation studies. Parameters like hematological analysis, percentage protection against mast cell degranulation, and time of occurrence of Pre-Convulsion Dyspnea (PCD) were calculated as the end point of the study. Further sections of the lung were prepared for histopathology analysis. In addition, in vitro, anti-oxidant studies were carried out to determine the percentage of inhibition of HAETI on oxidative stress parameters. After the assigned treatment to the group of animals with HAETI showed normalized hematological parameters, the bronchodilatation effect was confirmed by a significant (p<0.001) increase in the latency time of Pre Convulsion Dyspnoea (PCD) and pre-treatment with HAETI in mast cell degranulation study showed significant (p<0.001) reduction in degranulation of mesenteric mast cell number. The histopathological analysis of lung sections showed a reduction of total histological score in HAETI-treated guinea pigs compared with the disease control group (p< 0.0001). Based on IC50 values from in vitro assays, the free radical scavenging property of HAETI was confirmed due to the presence of active phytoconstituents. Based on the above findings, it was concluded that Tragia involucrata could be effectively used in the treatment of asthma and justified with traditional claims of the plant.

Effects of LTB4 receptor antagonism on pulmonary inflammation in rodents and non-human primates

Asthma, chronic obstructive pulmonary disease (COPD) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are characterized by neutrophilic inflammation and elevated levels of leukotriene B4 (LTB4). However, the exact role of LTB4 pathways in mediating pulmonary neutrophilia and the potential therapeutic application of LTB4 receptor antagonists in these diseases remains controversial. Here we show that a novel dual BLT1 and BLT2 receptor antagonist, RO5101576, potently inhibited LTB4-evoked calcium mobilization in HL-60 cells and chemotaxis of human neutrophils. RO5101576 significantly attenuated LTB4-evoked pulmonary eosinophilia in guinea pigs. In non-human primates, RO5101576 inhibited allergen and ozone-evoked pulmonary neutrophilia, with comparable efficacy to budesonide (allergic responses). RO5101576 had no effects on LPS-evoked neutrophilia in guinea pigs and cigarette smoke-evoked neutrophilia in mice and rats. In toxicology studies RO5101576 was well-tolerated. Theses studies show differential effects of LTB4 receptor antagonism on neutrophil responses in vivo and suggest RO5101576 may represent a potential new treatment for pulmonary neutrophilia in asthma.

Evidence that 13–14 di-hydro, 15-keto prostaglandin D2-induced airway eosinophilia in guinea-pigs is independent of interleukin-5

Prostaglandin D(2) (PGD(2)) has been shown to cause eosinophil, basophil and Th2 cell chemotaxis in vitro and in vivo through an action on the prostaglandin CRTH2 receptor. In the present study, the dependence of PGD(2)-induced eosinophil accumulation in vivo on interleukin-5 (IL-5) blood eosinophilia was investigated. Guinea-pigs were exposed to aerosols of 13,14di-hydro 15-keto PGD(2) (DK-PGD(2)) or platelet activating factor (PAF) and the eosinophil content of the bronchoalveolar lavage fluid or blood determined. In some experiments, DK-PGD(2) was administered systemically and eosinophilia measured. Aerosols of DK-PGD(2) caused eosinophil accumulation in the lungs 24h after exposure. DK-PGD(2) (10 microg x ml(-1)) -induced airway eosinophilia was inhibited when animals were treated with the CRTH2 receptor antagonist ramatroban. 1-4h after exposure to DK-PGD(2) a significant decrease in blood eosinophil count was measured. The anti-IL-5 antibody TRFK-5 had no inhibitory effect of DK-PGD(2)-induced airway eosinophilia, but abolished airway eosinophilia induced by exposure of guinea-pigs to aerosols of PAF. Intracardiac injection of DK-PGD(2) induced a dose-related increase in blood eosinophil numbers. It is concluded that, in the guinea-pig, DK-PGD(2)-induced airway eosinophilia is mediated by an action on prostaglandin CRTH2 receptors and that this response appears to be independent of IL-5.

Protective effects of cyclophosphamide, cyclosporin A and FK506 against antigen-induced lung eosinophilia in guinea-pigs.

A close association has been recognized between activated T cells and eosinophils in asthma, albeit circumstantial. The present study attempted to investigate this relationship in an animal model of lung eosinophilia using the new generation of T cell-selective immunosuppressants, cyclosporin A and FK506, compared with the myelotoxic immunosuppressive agent cyclophosphamide. Antigen challenge of ovalbumin-sensitized guinea-pigs resulted in a lung eosinophilia which was assessed by bronchoalveolar lavage. All three agents caused a marked suppression of lung eosinophilia at 24 h post-challenge when the compounds were administered at the time of sensitization but not when administered for 3 days before lavage. However, the lung eosinophilia at 72 h post-challenge was reduced significantly by FK506 and by cyclophosphamide, but not by cyclosporin A, when the drugs were administered for 3 days, before lavage. These results strongly suggest the involvement of T cells in antigen-induced late phase (72 h) eosinophilia in guinea-pigs but not at 24 h. The effects of cyclophosphamide were always associated with a reduction in circulating white cell counts, whereas cyclosporin A and FK506 showed no myelotoxic properties. These results suggest the potential therapeutic use of selective, non-cytotoxic immunosuppressive agents in asthma.

Antieosinophilic Activity of Orazipone

Orazipone is a novel sulfhydryl-reactive compound that has been previously shown to reduce lung eosinophilia in guinea pigs and rats and to inhibit degranulation in mast cells and cytokine production in monocytes and T-cells. However, the effects of orazipone on granulocyte longevity are unknown. Orazipone and its derivative 3-(4-chloro-3-nitro-benzylidene)-pentane-2,4-dione (OR-2370) reversed interleukin-5-afforded survival of human eosinophils by inducing apoptosis. In contrast, orazipone did not affect granulocyte macrophage-colony-stimulating factor-induced survival of human neutrophils. The effect of orazipone on eosinophil apoptosis is different from that of glucocorticoids in that even high con-centrations of interleukin-5 were not able to overcome the effect of orazipone. Orazipone further enhanced spontaneous apoptosis as well as that induced by CD95 ligation without inducing primary necrosis. OR-2370-induced DNA fragmentation was shown to be dependent on caspases 3 and 6 and c-jun-N-terminal kinase, whereas extracellular regulated kinase, p38 mitogen-activated protein kinase, and phosphatidylinositol 3-kinase as well as caspases 4, 8, and 9 seem not to mediate its actions. Our results suggest that orazipone and its derivative OR-2370 possess strong antieosinophilic activity and thus may have anti-inflammatory efficacy in the treatment of asthma and/or allergic conditions.

Pharmacology of a new cyclic nucleotide phosphodiesterase type 4 inhibitor, V11294

V11294 is a new cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor of the rolipram class. In this report we present the pharmacological profile of V11294. V11294 inhibited PDE4 isolated from human lung with IC 50 405 nM, compared to 3700 nM for rolipram. In contrast, V11294 inhibition of human PDE3 and PDE5 occurred only at concentrations greater than 100,000 nM. Like rolipram, V11294 inhibited PDE4D more potently than other PDE4 subtypes. V11294, when incubated with human anticoagulated whole blood in vitro, or administered to mice, caused increased cAMP concentration, consistent with inhibition of PDE4. V11294 inhibited lectin-induced proliferation and lipopolysaccharide-induced TNFα synthesis by human adherent monocytes in vitro and inhibited lipopolysaccharide-induced TNFα synthesis in mice. V11294 caused relaxation of guinea pig isolated trachea and inhibited allergen-induced bronchoconstriction and eosinophilia in guinea pigs at doses of 1 and 3 mg/kg, p.o. In ferrets, V11294 was not emetogenic at doses up to 30 mg/kg, p.o., despite plasma concentration reaching 10-fold the IC 50 for PDE4. In contrast, rolipram induced severe retching and vomiting at 10 mg/kg, p.o. In conclusion, V11294 is an orally active PDE4 inhibitor that exhibits antiinflammatory activity in vitro, and in vivo at doses that are not emetogenic.

Suppressive effects of F-1322 on the antigen-induced late asthmatic response and pulmonary eosinophilia in guinea pigs

We investigated the effects of F-1322 ( N-[2-[4-(benzhydryloxy)piperidino]ethyl]-3-hydroxy-5-(3-pyridylmethoxy)-2-naphthamide), a new compound that inhibits both thromboxane A 2 synthetase and 5-lipoxygenase and that functions as a histamine antagonist, on the Ascaris antigen-induced late asthmatic response and pulmonary eosinophilia in guinea pigs. Oral administration of F-1322 (10–100 mg/kg) inhibited the antigen-induced late asthmatic response in a dose-dependent manner. Histological analysis revealed that F-1322 prevented the accumulation of eosinophils in the airways and this was paralleled by a decrease in the number of eosinophils and lymphocytes recovered in bronchoalveolar lavage fluid. F-1322 (0.1–10 μM) inhibited eotaxin-induced chemotaxis and actin polymerization of eosinophils in vitro in a concentration-dependent manner, while oral administration of F-1322 dose-dependently suppressed the migration of eosinophils into the airways in vivo in response to infusion of interleukin 5 and eotaxin in combination. F-1322 may, thus, improve the late asthmatic response in this model, in part, by preventing the accumulation of eosinophils in the airways. The pharmacological profile of F-1322 indicates that this drug is likely to be useful in the treatment of allergic diseases such as asthma.

Allergen-induced bronchial eosinophilia in guinea-pigs is inhibited by both pre- and post-induction cyclosporin-A treatments

Repeated treatment of sensitized guinea-pigs with cyclosporin-A (CS-A) before aerosol allergen challenge is known to inhibit the subsequent bronchial eosinophilia. It is not known, however, if the drug is also effective on established/on-going bronchial eosinophilia. We have, therefore, studied the effect of CS-A on allergen-induced eosinophil recruitment into the bronchoalveolar lavage (BAL) fluid of guinea-pigs when given before or after induction. Ovalbumin-immunized guinea-pigs were treated with CS-A (20 mg/kg subcutaneously) or vehicle daily for varying periods before a single aerosol allergen challenge. In animals in which bronchial eosinophilia was maintained with repeated aerosol allergen challenge, CS-A or vehicle was given daily for varying periods after the first allergen challenge. BAL and cell count were performed 24 h after the last challenge. In vehicle-treated animals, a single allergen challenge caused a 4–5 fold increase in the number of eosinophils in the BAL fluid after 24 h, declining to baseline by 7 days. In repeatedly-challenged animals, this response was sustained throughout. Eosinophil infiltration was significantly inhibited when CS-A was given daily for 7–14 days, but not for 1 or 3 days, before allergen challenge. When given during an established/on-going eosinophil infiltration, a significant inhibition was seen after administration for 5 or 7 days, but not for 1 or 3 days. These results show that repeated CS-A administration inhibits not only the induction of allergic bronchial eosinophilia but also the maintenance of an established one. This may be relevant in the treatment of allergic diseases, such as asthma, in which drug administration often begins when eosinophilia is already established.

Effects of a Selective PDE4 Inhibitor, D-22888, on Human Airways and Eosinophils in vitro and Late Phase Allergic Pulmonary Eosinophilia in Guinea Pigs

The actions of a novel selective inhibitor of type 4 cyclic nucleotide phosphodiesterase (PDE4), D-22888, on human airway smooth muscle tone and human eosinophil respiratory burst in vitro and bronchoalveolar eosinophilia in allergen-challenged sensitized guinea pigs in vivo were assessed. D-22888 was a selective inhibitor of PDE4, exhibiting an IC50against human neutrophil PDE4 of 0.15 μm, compared to IC50values of 4.4 μmand 1.1 μmfor human platelet PDE3 and PDE5, respectively. D-22888 relaxed inherent tone in human bronchial rings in a concentration-dependent manner with an IC50of 5.0 μm(geometric mean, 95% ci 3.0–8.4 μm) and also caused a concentration-dependent inhibition of opsonized zymosan-induced superoxide anion generation by human eosinophils with an IC50of 3.1 μm(1.0–9.2 μm). Treatment of actively sensitized guinea pigs with single oral doses of D-22888 2 h before or 4 h after challenge reduced bronchoalveolar lavage (BAL) eosinophil numbers, 24 h after aerosol allergen challenge, by 48% and 73% at 10 mg/kg and 30 mg/kg, respectively, 2 h pre-challenge and 68% at 30 mg/kg 4 h post-challenge. Chronic twice-daily oral dosing with D-22888 for three days caused inhibition of 24 h post-challenge BAL eosinophilia, amounting to 88% at 30 mg/kg. These in vivo actions were comparable with those achieved with other selective PDE4 inhibitors and with the corticosteroid, dexamethasone. We conclude that D-22888 exerts actions on airway smooth muscle and eosinophil recruitment and activation that suggest that D-22888 may be a promising new drug for use in the treatment of allergic obstructive airways» diseases such as bronchial asthma.

O-82 - Effect of a peptide-leukotriene (p-LT) antagonist, pranlukast, on antigen-induced dual asthmatic response, and blood and lung eosinophilia in guinea pigs

O-82 - Effect of a peptide-leukotriene (p-LT) antagonist, pranlukast, on antigen-induced dual asthmatic response, and blood and lung eosinophilia in guinea pigs

Rapid and selective induction of blood eosinophilia in guinea pigs by recombinant human interleukin 5

Interleukin 5 (IL-5) has been implicated as a causal mediator in the development of pulmonary eosinophilia and airway hyperreactivity in human asthma. Supportive evidence for a pathogenic role of IL-5 in this disease has been provided by guinea pig models in which antigen-induced lung eosinophilia and bronchial hyperresponsiveness have been specifically attenuated with a neutralizing antibody to IL-5. In the present report, we describe a rapid mechanism-based model of IL-5-induced eosinophilia in the guinea pig. Our results show that intravenous injection of human IL-5 induced a 5-10-fold increase in the percentage and number of eosinophils in blood within 1 hour. In contrast, neutrophils and mononuclear cells were not recruited during this time. The increase in eosinophils was blocked by pretreatment of animals with an anti-IL5 monoclonal antibody (TRFK5) in doses similar to those which inhibit eosinophilia in guinea pig asthma models. Furthermore, dexamethasone, a potent inhibitor of eosinophilia in guinea pig asthma, profoundly suppressed the eosinophilia induced by human IL-5. This rapid model will be useful for elucidating the eosinophil activating properties of IL-5 in vivo and may potentially facilitate the development of IL-5 receptor antagonists for the specific blockade of the eosinophilic inflammation observed in human asthma.

Relationship between the development of bronchial hyperresponsiveness and the airway eosinophilia in guinea pigs following injection with Sephadex beads

Relationship between the development of bronchial hyperresponsiveness and the airway eosinophilia in guinea pigs following injection with Sephadex beads

Inhibition of Antigen-induced Pulmonary Eosinophilia and Neutrophilia by Selective Inhibitors of Phosphodiesterase Types 3 or 4 in Brown Norway Rats

Summary: Rolipram, a phosphodiesterase type 4 (PDE4)-selective inhibitor, has been demonstrated to inhibit antigen-induced pulmonary eosinophilia in guinea pigs and monkeys, suggesting that PDE4-selective inhibitors could be useful for treating asthma. Although the rat is used extensively in preclinical drug development, a pulmonary antiinflammatory effect of PDE4 inhibition has not been demonstrated in this species. Therefore, we examined the effects of rolipram, CI-930 (PDE3-selective inhibitor), zaprinast (PDE5-selective inhibitor) and aminophylline on antigen-induced pulmonary inflammatory cell influx in Brown Norway rats. Two weeks after sensitization rats were exposed to aerosolized ovalbumin and 24 h later bronchoalveolar lavage (BAL) was performed for determinations of total cell counts and cell type differentials. The resulting 10-fold increase in total cell counts was due primarily to an increase in eosinophils (from 0.06 to 11.0 × 10 6) and neutrophils (from 0.02 to 12 × 10 6). Rolipram, CI-930 and aminophylline, given p.o. before and after antigen challenge, each completely inhibited eosinophil influx, with B.I.D. ED 50 values of 0.5, 0.4 and 39 mg/kg, respectively. Rolipram, CI-930 and aminophylline each completely inhibited neutrophil influx as well, with B.I.D. ED 50 values of 0.1, 0.5 and 20 mg/kg, respectively. Denbufylline and milrinone (10 mg/kg p.o.) also inhibited eosinophil and neutrophil influx, consistent with PDE4 and PDE3 inhibition as the mechanisms of action of rolipram and CI-930, respectively. In contrast, zaprinast was inactive at 0.3-30 mg/kg. However, the β 2 agonist salbutamol greatly inhibited antigen-induced pulmonary eosinophilia and neutrophilia, with p.o. B.I.D. ED 50 values of 2.1 and 2.3 mg/kg, respectively, indicating that drugs which increase intracellular cAMP levels by one of several mechanisms can inhibit antigen-induced pulmonary inflammation in rats. In conclusion, these results demonstrate that PDE4 inhibitors produce pulmonary antiinflammatory effects in rats. Furthermore, these results suggest that PDE3 inhibitors also can produce pulmonary antiinflammatory effects in vivo.

P-487 - Allergen-induced asthmatic reactions with marked bronchial eosinophilia in guinea pigs and inhibitory effect of AL-3264, an anti-allergic agent.

P-487 - Allergen-induced asthmatic reactions with marked bronchial eosinophilia in guinea pigs and inhibitory effect of AL-3264, an anti-allergic agent.

Allergic bronchial eosinophilia: a therapeutic approach for the selection of potential bronchial anti-inflammatory drugs.

Aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) in guinea pigs was used as a marker of bronchial inflammation. Drugs were administered orally 4 h after aeroallergen challenge. Allergic bronchial eosinophilia in guinea pigs was inhibited by orally administered dexamethasone and methylprednisolone. Terfenadine (a newer H1-receptor antagonist), theophylline (a nonspecific phosphodiesterase inhibitor), and salbutamol (a beta 2-agonist) did not influence allergic eosinophilic infiltration. Many of these agents, administered prophylactically, have been reported to suppress allergic eosinophilic infiltration in the BALF of guinea pigs. Methylprednisolone, a steroid, inhibits allergic bronchial eosinophilia regardless of the time of administration; that is, 2 h before or 4 h after aeroallergen challenge. The therapeutic approach used in this study may facilitate drug discovery for bronchial inflammation/asthma.

Induction of lung eosinophilia and neutrophilia in guinea pigs following injection of sephadex beads.

We have developed a method of induction of airway eosinophilia and neutrophilia in guinea pigs by intravenous injection of various types of Sephadex beads. In the first series of experiments, we have shown that G-50 Sephadex beads (Superfine, 24 mg/kg in conscious animals) induced a large accumulation of inflammatory cells in alveolar walls. The bronchoalveolar lavage (BAL) fluid from animals treated with this dose of Sephadex beads contained about 85 x 10(6) cells as compared to 20 x 10(6) cells in control animals. The eosinophils corresponded to 41% of the BAL cell population as assessed with Wright-Giemsa staining. However, in the BAL fluid from these bead-treated animals, a significant increase of monocytes, lymphocytes, and neutrophils was also observed. We have also tested the potency of G-75, G-100, and G-200 Sephadex beads (Superfine) to induce eosinophilia in guinea pig. Nonlethal intravenous doses of G-75 (14.27 mg/kg), G-100 (8.0 mg/kg), and G-200 (10.71 mg/kg) Sephadex beads were selected and induced variable levels of airway eosinophilia and neutrophilia in conscious guinea pigs. The percentage of eosinophil recovered in the BAL fluid corresponded to 35, 61, and 44% of total cells for G-75, G-100, and G-200, respectively. The neutrophils corresponded to 24, 2, and 12% of the total BAL cells for G-75, G-100, and G-200, respectively. Since the size of the beads did not seem to correlate with the intensity of airway eosinophilia and neutrophilia, the effect of lower doses of the G-50 Sephadex beads (9.86-0.43 mg/kg) on the inflammatory cell infiltration was also tested. Results showed that there was a correlation between the neutrophil number and the number of beads (r = 0.996), whereas the number of eosinophils was less directly correlated to the bead number (r = 0.812). The alveolar eosinophils were purified from BAL fluid by centrifugation on a continuous Percoll gradient (65%) to separate eosinophils from neutrophils. Normodense eosinophils (density 1.087-1.100 g/ml) obtained from Sephadex-treated animals were found at the bottom of the continuous Percoll gradient (25 x 10(6); 98% purity). These highly purified eosinophils released thromboxane A2 (TxA2) following stimulation with 2 microM ionophore A23187. The method of accumulation and purification of guinea pig alveolar eosinophils is simple, rapid, and provides a large number of pure normodense cells for further biological studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of MKS-492 on Antigen-Induced Bronchoconstriction and Allergic Reaction in Guinea Pigs and Rats

Effects of R[+]-8-([1-[3,4-dimethoxyphenyl]-2-hydroxyethyl]amino) -3,7-dihydro-7-[2-methoxyethyl]-1,3-dimethyl-1H-purine-2,6-dione (MKS-492), a reported type III isozyme inhibitor of cyclic nucleotide phosphodiesterase, on antigen- or platelet activating factor (PAF)-induced bronchoconstriction and allergic reactions in guinea pigs and rats were investigated. 1) MKS-492 inhibited antigen-induced bronchoconstriction in guinea pigs. Aminophylline also inhibited the reaction. 2) MKS-492 inhibited PAF-induced bronchoconstriction and inhibited the increase in airway responsiveness to histamine in guinea pigs, although aminophylline failed to affect these reactions. 3) MKS-492 relaxed guinea pig tracheal muscle in vitro more potently than aminophylline. 4) MKS-492 inhibited leukotriene B4 (LTB4)-induced airway eosinophilia in guinea pigs. 5) MKS-492 inhibited passive cutaneous anaphylaxis and mediator-induced skin reactions in rats more potently than aminophylline. Both drugs inhibited antigen- and phospholipase A2-induced histamine release from guinea pig lung tissue. 6) MKS-492 inhibited PAF-induced O2- generation from guinea pig alveolar macrophages. These results indicate that MKS-492 is a more potent inhibitor of allergic bronchoconstriction and PAF- or LTB4-induced inflammatory reactions in guinea pigs and the allergic cutaneous reactions in rats when compared to aminophylline.

Anti-IL-5 monoclonal antibody inhibits allergic late phase bronchial eosinophilia in guinea pigs: a therapeutic approach

In this study the effect of purified rat anti-mouse IL-5 monoclonal antibody on aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid of guinea pigs was studied. The i.p. injection of anti-IL-5 antibody 4 h after aeroallergen challenge inhibited eosinophil infiltration in a dose-dependent fashion. The resulting ED 50 was 10 (3.4–32.8) μg/kg. The clinical therapeutic usefulness of anti-IL-5 or anti-IL-5-producing cells in asthma/allergy treatment remains to be an intriguing possibility.

Repeated antigen challenge induces airway hyperresponsiveness with tissue eosinophilia in guinea pigs

To test the hypothesis that the development of airway hyperresponsiveness (AHR) lasting greater than or equal to 3 days after the last antigenic exposure required repeated mediator release, we compared dose-response changes in lung resistance (RL) to acetylcholine (ACh) in animals sensitized with 1% ovalbumin (OA), 4% Bordatella pertussis aerosol and subsequently challenged with 0.5% OA aerosol twice weekly for 4-6 wk vs. animals receiving saline aerosol instead of OA. Despite antihistamine pretreatment, each OA challenge produced cyanosis and inspiratory indrawing. Blood gas analysis in six guinea pigs revealed an immediate fall in arterial PO2 (PaO2) from 104.3 +/- 4.9 to 35.4 +/- 2.2 Torr after a 1-min exposure to aerosolized OA. ACh dose-response measurements of RL 3 days after the last OA challenge demonstrated a leftward shift and an increased magnitude of response. These differences were less marked at 7 days, and by 14 days after the last OA challenge, ACh dose-response curves were not different from those of control guinea pigs. Sensitization without repeated antigen challenge did not cause hyperresponsiveness. Morphometric analysis showed significantly increased numbers of eosinophils in the epithelium of airways in hyperresponsive guinea pigs, without neutrophil infiltration or alterations in epithelium and airway wall areas. We conclude that repeated antigenic challenge, but not sensitization alone, causes prolonged AHR in guinea pigs, which is associated with tissue eosinophilia.

Effect of levamisole on the course of experimental leishmaniasis in guinea-pigs and mice: haematological and immunological findings.

The effects of levamisole on the course of Leishmania enriettii infection in guinea-pigs and L. major in mice were investigated. It was demonstrated that levamisole-treated guinea-pigs either did not develop an ulcerative lesion or developed a much smaller lesion than untreated animals. Moreover, metastases which are commonly produced in approximately 50% of animals receiving 2 x 10(6) L. enriettii did not occur in levamisole-treated guinea-pigs. Leishmania enriettii infection usually causes leukopenia and eosinophilia in guinea-pigs approximately two to three weeks after infection. These haematological changes did not occur in animals receiving levamisole. The percentage of rosette T-cells which diminished in the L. enriettii infection was normalized in the group of levamisole-treated and infected guinea-pigs. The severity of Leishmania infection in mice receiving levamisole was lower in comparison to a control group of the animals.