Pulmonary Eosinophilic Infiltration Research Articles

An inverted papilloma isolated to the sphenoid sinus in a pediatric patient

Chelidonine, a major bioactive, isoquinoline alkaloid ingredient in Chelidonium majus, exhibits anti-inflammatory and other pharmacological properties. However, its molecular mechanisms in asthma remain unclear. In this work we investigated chelidonine's effect and mechanism in airway inflammation in a mouse model of allergic asthma.The mice were sensitized to ovalbumin followed by aerosol allergen challenges and determination of chelidonine's effect on enhanced pause (Penh), pulmonary eosinophilic infiltration, eotaxin-2, interleukin-4 (IL-4), IL-13, OVA-specific IgE production, and several transcription factors.Chelidonine strongly suppressed airway eosinophilia, expression of eotaxin-2, IL-4, and IL-13 cytokine production in bronchoalveolar lavage fluid (BALF). It also attenuated lung IL-17, and eotaxin-2 mRNA expression levels. Moreover, it suppressed eotaxin-2 and IL-17 production in accordance with up- and downregulation of forkhead box p3 (Foxp3), and signal transducer and activator of transcription (STAT6) expression, respectively.Chelidonine has profound inhibitory effects on airway inflammation and this effect is caused by suppression of IL-4, eotaxin-2, and OVA-specific IgE production through the STAT6 and Foxp3 pathways. So chelidonine can improve allergic asthma in mice and be a novel anti-asthma therapeutic.

Eosinophile Pneumonie als unerwünschte Arzneimittelwirkung

Eosinophilic pneumonia is a lung disorder characterized by eosinophilic pulmonary infiltration and blood eosinophilia. It can be caused by a variety of drugs. Especially in mild forms and in chronically neurologically ill patients, it can be difficult to spot. We report the case of a 46-year-old woman suffering from multiple sclerosis who developed nitrofurantoin-induced eosinophilic pneumonia.

Preexposure to Amorphous Silica Particles Attenuates but also Enhances Allergic Reactions in Trimellitic Anhydride-Sensitized Brown Norway Rats

Irritant-induced inflammation of the airways may aggravate respiratory allergy induced by chemical respiratory allergens. Therefore, the effect of airway irritation by synthetic amorphous silica (SAS) on respiratory allergy to trimellitic anhydride (TMA) was studied. Brown Norway (BN) rats were topically sensitized on day 0 and on day 7, subsequently exposed for 6 h/day for 6 days to 27 mg/m3 SAS, and challenged by inhalation to a minimally irritating concentration of 12 mg/m3 TMA, 24 h after the last SAS exposure. An additional group was exposed to SAS before a second challenge to TMA. Control groups were treated with vehicle, and/or did not receive SAS exposure. Breathing parameters, cellular and biochemical changes in bronchoalveolar lavage (BAL) fluid, and histopathological airway changes 24 h after challenge were the main parameters studied. Exposure to SAS alone resulted in transient changes in breathing parameters during exposure, and in nasal and alveolar inflammation with neutrophils and macrophages. Exposure to SAS before a single TMA challenge resulted in a slightly irregular breathing pattern during TMA challenge. SAS also diminished the effect of TMA on tidal volume, laryngeal ulceration, laryngeal inflammation, and the number of BAL (lung) eosinophils in most animals, but aggravated laryngeal squamous metaplasia and inflammation in a single animal. The pulmonary eosinophilic infiltrate and edema induced by a second TMA challenge was diminished by the preceding SAS exposure, but the number of lymphocytes in BAL was increased. Thus, a respiratory particulate irritant like SAS can reduce as well as aggravate certain aspects of TMA-induced respiratory allergy.

Non allergic simple eosinophilic pneumonia: Löffler syndrome: A case report study

Löffler syndrome is an acute, pneumonia of unknown ethiology. This disease is not often associated with bronchial asthma. In its asymptomatic form, this disease is reversible, transient, self-limited with no requests for specific therapy regimen. In the symptomatic form, as well as during its progression, treatment with steroids is very effective. Furthermore, in both acute eosinophilic and idiopathic chronic eosinophilic form, this kind of therapy ensures survival. The case of a 53-year-old Caucasian woman was presented with 2-month history of low grade fever, shortness of breath, cough and reduced exercise tolerance. Although she had an allergic accident on insects in history, non allergy reactions as well as an obstructive disease with that kind of origin were not detected on admission. The diagnosis of simple eosinophilic pneumonia (SEP) (Löffler's syndrome) was confirmed by transbronchial biopsy and by sternal testing. The peripheral blood eosinophilia with pulmonary eosinophilic infiltrates on X ray chest radiography were observed during clinical examination. Biopsy specimen of the lung parenchym showed changes associated with Löffler's syndrome. The diagnosis was, also, confirmed according to the radiographic findings of unilateral migratory infiltrates consistent pneumonia. Churg Strauss syndrome (CSS) has to be considered in this differential diagnosis. Frequently, this disease has extrinsic bronchial asthma with eosinophilic pneumonia in history: asthma is often associated with allergic bronchopulmonary aspergillosis. In the reported case, treatment with steroids resulted in a marked clinical improvement compared to nonsteroid therapy.

A Case of Posttraumatic Pleural Effusion with Peripheral Eosinophilia

Eosinophilic pleural effusions (EPE) are defined as those effusions that contain at least 10% eosinophils, and EPE can be associated with peripheral blood eosinophilia in a varie ty of systemic diseases. There have been a few cases that have addressed the association of peripheral blood eosinophilia and posttraumatic EPE, and this condition can be misdiagnosed as being the result of other causes due to the delayed presentation. We report here on a case of 47-year-old male who presented with eosinophilic pleural effusion associated with peripheral blood eosinophilia at 2 months after minor chest trauma. We excluded the other possible causes such as consumption of drugs, parasite infection, malignancy, diseases of pulmonary eosinophilic infiltration, autoimmune diseases and pulmonary thromboembolism. We observed his clinical course without specific treatment. Three months later, the pleural effusion completely disappeared and the number of peripheral eosinophils returned to normal. (Tuberc Respir Dis 2008;64:379-382)

Index of Suspicion

Index of Suspicion

Leukozytoklastische eosinophile Vaskulitis bei eosinophilem Lungeninfiltrat „Löffler“

Histologically, leukocytoclastic vasculitis (LV) presents with neutrophilic granulocytes with leukocytoclasia and erythrocyte extravasation, associated with variable counts of lymphocytes, plasma cells and eosinophilic granulocytes. The association of a LV with eosinophilic granulocytes and eosinophilic pneumonia was first described by Chan et al. in 1982. Our case represents the second report in the literature of this rare disease: a 85 year old patient with LV and numerous eosinophilic granulocytes in association with intermittent blood eosinophilia and Löffler syndrome (eosinophilic pulmonary infiltrates). The recurrent episodes were treated successfully with oral corticosteroids.

Organizing Pneumonia and Pulmonary Eosinophilic Infiltration Associated with Daptomycin

To report a case of organizing pneumonia with pulmonary eosinophilic infiltrates in a patient receiving daptomycin. An 84-year-old man developed bilateral, irregularly shaped nodules and infiltrates in the mid and peripheral lung and multiple mediastinal lymph nodes following treatment with intravenous daptomycin for infection of his left knee prosthesis. His other symptoms included decreased appetite, weight loss (6.8 kg over 4-6 wk), malaise, and generalized weakness after 4 weeks of daptomycin therapy. Transthoracic needle biopsy revealed organizing pneumonia with scattered eosinophils. His symptoms and results of computed tomography (CT) scan improved in the month following discontinuation of daptomycin. The Naranjo probability scale indicated a probable reaction to daptomycin. Pulmonary reactions have been reported with numerous drugs and have a wide range of clinical and radiographic presentations. Clinical trials have shown that daptomycin is well tolerated and has an adverse effect profile similar to that of vancomycin and the semisynthetic penicillins. This case report suggests that chronic use of daptomycin caused organizing pneumonia with eosinophilic infiltrates in a patient treated for an infected knee prosthesis. A definite mechanism for this reaction is not known. We speculate that the chronic administration of daptomycin allowed drug accumulation in surfactant in the alveolar spaces. This may result in higher concentrations of drug near the alveolar epithelial surface, which could injure the epithelium, resulting in organizing pneumonia. Development of new pulmonary infiltrates in patients treated with chronic daptomycin therapy should alert healthcare workers to this potential association.

C57Bl/6 mice are protected from respiratory syncytial virus (RSV) challenge and IL-5 associated pulmonary eosinophilic infiltrates following intranasal immunization with Protollin-eRSV vaccine

The protective efficacy of an intranasal (IN) Protollin-eRSV vaccine has recently been demonstrated in the RSV-susceptible BALB/c mouse model. Here, we report the safety, immunogenicity and efficacy of Protollin-eRSV vaccine in the relatively resistant C57Bl/6 mouse model. C57Bl/6 mice immunized IN with either two or three doses of Protollin-eRSV produced significant systemic and mucosal RSV-specific antibodies. Mice immunized with the Protollin vaccine displayed polarized Th1 responses with augmented IFNγ/IL-5 ratios in RSV-restimulated lung and spleen cell preparations compared with animals that received antigen alone. The Protollin-eRSV immunized C57Bl/6 mice were fully protected against challenge without eosinophilic pulmonary pathology observed in the animals immunized with the formalin-inactivated RSV vaccine. This new model will permit us to dissect the respective roles of the TLR2 and TLR4 ligands contained in the vaccine using TLR knock-out animals established on the C57Bl/6 background.

Inhalation of Concentrated Ambient Particulate Matter Near a Heavily Trafficked Road Stimulates Antigen-Induced Airway Responses in Mice

Motor vehicle exhaust emissions are known to exacerbate asthma and other respiratory diseases. Several studies have demonstrated significant associations between living near highly trafficked roadways and increased incidence of asthma and increased severity of asthma-related symptoms, medication usage, and physician visits. This study tested the hypotheses that (1) exposure to particulate matter (PM) near a heavily trafficked Los Angeles freeway would enhance inflammatory and allergic responses in ovalbumin (OVA)-sensitized BALB/c mice compared to sensitized, clean air controls, and (2) there would be differences in response at two distances downwind of heavily traveled freeways because of greater toxicity of PM closest to the freeway. An ambient particle concentrator was used to expose ovalbumin (OVA)-treated BALB/c mice to purified air, to concentrated fine ambient particles, and to concentrated ultrafine airborne particles (CAPs) at 2 distances, 50 m and 150 m, downwind of a roadway that is impacted by emissions from both heavy-duty diesel and light duty gasoline vehicles. Tissues and biological fluids from the mice were analyzed after exposures for 5 days/wk in 2 consecutive weeks. The biomarkers of allergic or inflammatory responses that were assessed included cytokines released by Type 2 T-helper cells (interleukin [IL]-5 and IL-13), OVA-specific immunoglobulin E (IgE), OVA-specific immunoglobulin G1 (IgG1), and pulmonary infiltration of polymorphonuclear leukocytes and eosinophils. IL-5 and IgG1 were significantly increased in mice exposed to CAPs 50 m downwind of the road, compared to responses in mice exposed to purified air, providing evidence of allergic response. No significant increases in allergy-related responses were observed in mice exposed to CAPs 150 m downwind of the road. The biological responses at the 50-m site were significantly associated with organic and elemental carbon components of fine and ultrafine particles (p ≤ .05). The primary source of these contaminants at the roadway sites was motor vehicle emissions, suggesting that particulate matter from motor vehicle fuel combustion could exert adjuvant effects and promote the development of allergic airway diseases.

Adenovirus expressing interleukin-1 receptor antagonist alleviates allergic airway inflammation in a murine model of asthma

Interleukin-1 (IL-1) is a proinflammatory cytokine and IL-1 receptor antagonist (IL-1ra) is a natural inhibitor that binds to IL-1 receptor type I without inducing signal transduction. It is suggested that IL-1 is required for allergen-specific T helper type 2 cell activation and the development of airway hyper-responsiveness (AHR), but the immunologic effect of exogenous IL-1ra in allergic asthma remains unclear. To examine the effect of IL-1ra on airway inflammation and immunoeffector cells in allergic asthma, recombinant adenovirus expressing human IL-1ra (Ad-hIL-1ra) was delivered intranasally into ovalbumin (OVA)-immunized mice. Single intranasal administration of Ad-hIL-1ra before airway antigen challenge in OVA-immunized mice significantly decreased the severity of AHR and reduced pulmonary infiltration of eosinophils and neutrophils. Suppression of IL-5 and eotaxin with concomitant enhancement of interferon gamma in bronchoalveolar lavage fluid was also noted in OVA-immunized mice by administration of Ad-hIL-1ra. In addition, histological studies showed that Ad-hIL-1ra was able to decrease OVA-induced peribronchial inflammation. Taken together, our results indicated that administration of Ad-hIL-1ra may have therapeutic potential for the immunomodulatory treatment of allergic asthma.

AttenuatedSalmonella typhimuriumreduces ovalbumin-induced airway inflammation and T-helper type 2 responses in mice

Cytokines produced by Th2 cells are responsible for the pathogenesis of asthma. Th1-biased immune responses caused by attenuated salmonella have the potential to relieve asthmatic symptoms. We evaluated whether oral administration of attenuated salmonella could modulate allergic responses in a chicken ovalbumin (OVA)-induced asthmatic murine model. Mice were fed with attenuated salmonella SL7207 one dose before and three doses during the induction of an allergic response. Lung histology, percentages of eosinophil in bronchoalveolar lavage fluid, serum levels of OVA-specific antibodies and cytokine production by OVA-activated splenocytes were evaluated in mice with or without the administration of SL7207. A significant reduction in pulmonary eosinophilic infiltration was observed in mice receiving attenuated salmonella. Lower levels of OVA-specific IgG1 but higher titres of OVA-IgG2a in serum were also detected in this group. Splenocytes from salmonella-fed mice produced lower levels of Th2 cytokines upon OVA stimulation. The administration of attenuated salmonella significantly suppressed immunopathological symptoms in OVA-sensitized mice. Inhibition of Th2 responses might explain the potential mechanisms. This study provides some evidence for the feasibility of attenuated salmonella as an effective vaccine for allergic diseases.

End Organ Effects of High-Dose Human Equivalent Methylprednisolone in a Spinal Cord Injury Rat Model

Interventional study. To analyze the histologic effects of high-dose human equivalent methylprednisolone on the pulmonary, cardiac, intestinal, renal, hepatic, and splenic tissues in a spinal cord injury rat model. There are numerous investigations of various medical interventions for the treatment of acute spinal cord trauma. Currently, the only generally accepted medical intervention in an acute spinal cord trauma is the intravenous administration of high doses of methylprednisolone. Although it has been nearly 2 decades since the first National Acute Spinal Cord Injury Study investigated the role high-dose steroids might play in the treatment of acute spinal cord trauma, controversy still exists regarding the efficacy of this treatment. To our knowledge, no study has examined the role of high-dose methylprednisolone in organ systems other than the spinal cord in an acute spinal cord injury model at the histologic level. This study attempts to characterize end organ histologic response to human dose equivalent (HDE) intravenous methylprednisolone administration in a rodent model of acute spinal cord injury. A total of 48 Sprague-Dawley rats were divided equally into control and experimental groups. Each group was subdivided into 6 sets of 4 animals each, according to intervals after injury. Groups 1-6 consisted of animals euthanized at 0, 4, 8, 16, 24, and 48 hours after spinal cord injury. Paraplegia after lower thoracic laminectomy was achieved using a standardized Allen weight drop technique. Within 1 hour of injury, experimental animals were treated with HDE methylprednisolone, infused for 23 hours continuously. Liver, kidney, lung, intestine, spleen, and heart were harvested at variable intervals after injury and prepared for histologic examination. These slides were analyzed with microscopic staining techniques and compared in a blinded manner by a qualified pathologist. Of all the end organs analyzed, the spleens were most affected. Lymphocytic depletion was seen in as little as 4 hours after methylprednisolone infusion and continued until 48 hours. Pulmonary tissues variably showed interstitial congestion and eosinophilic alveolar collections. Intestinal mucosal tissues showed edema and autolyzed mucosa from 16 hours onwards. Cardiac, kidney, and hepatic tissue did not differ significantly from controls. Histologically, HDE methylprednisolone caused significant splenic lymphocytic depletion changes in as little as 4 hours. This trend of end organ lymphocytopenia continued to progress until 48 hours. Pulmonary eosinophilic infiltrates were seen from 8 until 24 hours. Intestinal mucosal edema and necrosis were seen in samples at 16 hours throughout 48 hours. This study was designed to evaluate end organ changes seen in an animal model of an acute spinal cord injury treated with HDE methylprednisolone. Study animals were infused with HDE methylprednisolone given according to the National Acute Spinal Cord Injury Study II protocol. The kidney, lung, cardiac, intestinal, splenic, and hepatic tissues from the aforementioned animals were then sectioned and analyzed using histologic staining techniques by a qualified pathologist.

Exacerbation of Experimental Allergic Asthma by Augmented Th2 Responses in WSX-1-Deficient Mice

WSX-1 (IL-27R) is a class I cytokine receptor with homology to gp130 and IL-12 receptors and is typically expressed on CD4+ T lymphocytes. Although previous reports have clarified that IL-27/WSX-1 signaling plays critical roles in both Th1 differentiation and attenuation of cell activation and proinflammatory cytokine production during some bacterial or protozoan infections, little is known about the importance of WSX-1 in cytokine-mediated diseases of allergic origin. To this aim, we took advantage of WSX-1-deficient (WSX-1(-/-)) mice and induced experimental asthma, in which Th2 cytokines are central modulators of the pathology. OVA-challenged WSX-1(-/-) mice showed marked enhancement of airway responsiveness with goblet cell hyperplasia, pulmonary eosinophil infiltration, and increased serum IgE levels compared with wild-type mice. Production of Th2 cytokines, which are largely responsible for the pathogenesis of asthma, was augmented in the lung or in the culture supernatants of peribronchial lymph node CD4+ T cells from WSX-1(-/-) mice compared with those from wild-type mice. Surprisingly, IFN-gamma production was also enhanced in WSX-1(-/-) mice, albeit at a low concentration. The cytokine overproduction, thus, seems independent from the Th1-promoting property of WSX-1. These results demonstrated that IL-27/WSX-1 also plays an important role in the down-regulation of airway hyper-reactivity and lung inflammation during the development of allergic asthma through its suppressive effect on cytokine production.

Clinical findings of eosinophilic otitis media

Objectives: Eosinophilic otitis media is a new entity representing intractable otitis media with viscous middle ear discharge containing eosinophils. However, the etiological background remains to be obscure. Aiming at an assessment of the clinical findings, cases of the eosinophilic otitis media at the outpatient clinics in Kyushu University Hospital were retrospectively reviewed. Methods: When middle ear discharge of patients with a complaint of intractable otorrhea and hearing loss was viscous, an infiltration of eosinophils into otorrhea was examined. In case of positive findings, further assessment was performed. Results: There were 5 males and 9 females, ranging in age from 38 to 70 years (average, 53) old; 71% were affected in bilateral ear. Allergic diseases, such as bronchial asthma, pulmonary eosinophilic infiltration and nasal polyp was complicated at 79%, 14%, and 43% of all patients, respectively. The blood eosinophil increased. Total serum IgE level was within normal range except one. RAST showed positive in 6. In contrast to the eosinophilic nasal polyp, eosinophilic infiltration in middle ear mucosa was not observed in 5 of 7 specimens. Aural polyp formation has a significant correlation to an initial onset age and neither blood eosinophil count nor illness period. Conclusion: Elevation of eosinophils in blood, no specific serum IgE, and middle ear antigen indicated that eosinophilic otitis media is one of the eosinophil-related disease. Aural polyp formation is not related to an infiltration of eosinophils like eosinophilic nasal polyp.

Respiratory syncytial virus, pneumonia virus of mice, and influenza A virus differently affect respiratory allergy in mice.

Respiratory viral infections in early childhood may interact with the immune system and modify allergen sensitization and/or allergic manifestations. In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic T helper (Th) 2 immune response, characterized by the production of IL-4, IL-5, and IL-13, and inflammatory infiltrates. However, it is unclear whether the RSV-enhanced respiratory allergic response is a result of non-specific virus-induced damage of the lung, or virus-specific immune responses. In the present study we investigated whether RSV, pneumonia virus of mice (PVM) and influenza A virus similarly affect the allergic response. BALB/c mice were sensitized and challenged with ovalbumin (OVA), and inoculated with virus during the challenge period. Pulmonary inflammation, lung cytokine mRNA responses, and IgE production in serum were assessed after the last OVA-challenge. Like RSV, PVM enhanced the OVA-induced pulmonary IL-4, IL-5, and IL-13 mRNA expression, which was associated with enhanced perivascular inflammation. In addition, PVM increased the influx of eosinophils in lung tissue. In contrast, influenza virus decreased the Th2 cytokine mRNA expression in the lungs. However, like PVM, influenza virus enhanced the pulmonary eosinophilic infiltration in OVA-allergic mice. The Paramyxoviruses RSV and PVM both are able to enhance the allergic Th2 cytokine response and perivascular inflammation in BALB/c mice, while the Orthomyxovirus influenza A is not.

Vegetating Iododerma and Pulmonary Eosinophilic Infiltration. A Simple Co-occurrence?

Vegetating Iododerma and Pulmonary Eosinophilic Infiltration. A Simple Co-occurrence?

Blockade of Inflammation and Airway Hyperresponsiveness in Immune-sensitized Mice by Dominant-Negative Phosphoinositide 3-Kinase–TAT

Phosphoinositide 3-kinase (PI3K) is thought to contribute to the pathogenesis of asthma by effecting the recruitment, activation, and apoptosis of inflammatory cells. We examined the role of class IA PI3K in antigen-induced airway inflammation and hyperresponsiveness by i.p. administration into mice of Δp85 protein, a dominant negative form of the class IA PI3K regulatory subunit, p85α, which was fused to HIV-TAT (TAT-Δp85). Intraperitoneal administration of TAT-Δp85 caused time-dependent transduction into blood leukocytes, and inhibited activated phosphorylation of protein kinase B (PKB), a downstream target of PI3K, in lung tissues in mice receiving intranasal FMLP. Antigen challenge elicited pulmonary infiltration of lymphocytes, eosinophils and neutrophils, increase in mucus-containing epithelial cells, and airway hyperresponsiveness to methacholine. Except for modest airway neutrophilia, these effects all were blocked by treatment with 3–10 mg/kg of TAT-Δp85. There was also significant reduction in IL-5 and IL-4 secretion into the BAL. Intranasal administration of IL-5 caused eosinophil migration into the airway lumen, which was attenuated by systemic pretreatment with TAT-Δp85. We conclude that PI3K has a regulatory role in Th2-cell cytokine secretion, airway inflammation, and airway hyperresponsiveness in mice.

A single amino acid substitution in a recombinant G protein vaccine drastically curtails protective immunity against respiratory syncytial virus (RSV)

Recent studies have indicated a dominant T cell epitope located approximately between amino acids 184 and 203 on the respiratory syncytial virus (RSV) G protein. Using an Escherichia coli-grown plasmid vector encoding a fragment of thioredoxin (Trx) fused to a central region (amino acids 128–229) of the RSV G protein, we employed site-directed mutagenesis to investigate the importance of selected amino acids on vaccine efficacy. By changing two amino acids Arg188 and Lys192 to alanine, the ability of the Trx-G128–229 fusion protein to protect mice against RSV challenge was virtually abolished. Mice immunized with the double mutant protein showed low levels of neutralizing antibodies and no pulmonary eosinophilic infiltrate, in contrast to that observed in mice immunized with wild type protein prior to RSV challenge. While less effective than the double mutant, mutation of either Arg188 or Lys192 to Ala drastically impaired the ability of immunized Trx-G128–229 to induce neutralizing antibodies and to elicit pulmonary eosinophilia associated with RSV challenge. Despite low levels of virus-neutralizing antibodies, G protein-specific antibodies were detected by Western blotting in the sera from mice immunized with either of the single mutants (Arg188 or Lys192) but not the double mutant. Finally, immunization of mice with truncated forms of the Trx-G protein, showed partial protection against RSV challenge with Trx-G128–188 but not with Trx-G189–229. Taken together, the results indicate an important role for Arg188 and Lys192 in the induction of protective immunity and priming for eosinophilia against RSV. Furthermore, while the dominant protective linear epitope on the RSV G protein requires an intact sequence around Arg188, there are additional, but less potent, protective epitopes upstream of Arg188.

Respiratory syncytial virus enhances respiratory allergy in mice despite the inhibitory effect of virus-induced interferon-gamma.

In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic Th2 immune response, characterised by production of interleukin (IL)-4, IL-5, and IL-13, and eosinophilic inflammation. This enhancement of the Th2 response occurs simultaneously with a strong RSV-induced Th1 cytokine response (IL-12 and IFN-gamma). The present study investigated whether IFN-gamma and IL-12 are critically involved in this RSV-enhanced OVA allergy. Therefore, IFN-gammaR- and IL-12-deficient mice (both on a 129/Sv/Ev background) were sensitised and challenged with ovalbumin (OVA) and infected with RSV during the OVA challenge period. Neither gene deletion affected the development of ovalbumin-induced allergic inflammation in mice. However, when OVA-allergic IFN-gammaR deficient mice were infected with RSV, an increased pulmonary eosinophilic infiltrate and increased IL-4 and IL-13 mRNA expression in lung tissue were observed compared with identically treated wild-type mice. In contrast, deficiency of IL-12 did not aggravate the Th2 immune and inflammatory response in OVA/RSV-treated mice, compared with wild-type. In conclusion, the virus-induced IFN-gamma response diminishes the Th2 inflammatory response during OVA allergy but fails to prevent totally the enhancement of the OVA allergy by RSV. In contrast, IL-12 is not involved in inhibiting nor increasing the RSV-enhanced allergy in 129/Sv/Ev mice.