Se presenta el caso de un varón de cuatro años y medio con toxocariosis atípica, procedente de La Matanza, Morropón, Piura. El paciente presentó síntomas inespecíficos durante nueve días; la sospecha de toxocariosis derivó del hallazgo de eosinofilia periférica marcada (15% ó 1470 células/μL) en el hemograma. El diagnóstico se confirmó por serología mediante el método de enzimoinmunoanálisis (ELISA) demostrando la presencia de anticuerpos anti-Toxocara de tipo IgG, así como de tipo IgM. El cuadro se autolimitó antes de que el paciente recibiera tratamiento con albendazol 15mg/ kg/día durante cinco días. / We present the case of a 4.5 years old boy with atypic toxocariasis, from La Matanza, Morropon, Piura. The patient had non-specific symptoms during 9 days. Suspicion of Toxocariasis was supported by marked eosinophilia in the cell blood count (15% or 1470 cells/μL). Diagnosis was confirmed by laboratory with ELISA serology demonstrating the presence of IgG and IgM anti-Toxocara antibodies. Symptoms receded before the patient received a five-day treatment with albendazol 15mg/kg/day.

Zhang Jiping. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 157-179). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

The role of eosinophilia in allergic disorders indicates hIL-5 as a target of therapy. The conservation of hIL-5 proximal elements suggests they are important in controlling expression. Corticosteroids are important in the treatment of allergy, and are powerful inhibitors of IL-5 expression. Antisense oligonucleotides are new compounds that can specifically inhibit IL-5 production. This study aimed at understanding the role of conserved lymphokine element 0 (CLEO) in induction and inhibition of IL-5.The conserved proximal CLEO/TATA elements driving a luciferase reporter gene gave higher expression than a 500bp promoter in PER1 17 T-cell line. Two and three copies of IL-5 CLEO upstream of the silent IL-4 minimal promoter gave 150-200 fold increases in expression in forward orientation, but little activity in reverse orientation. Consequently, while CLEO is a powerful activator, it is not a classical enhancer. Antisense technology has also shown the dependence of IL-5 gene transcription on the de novo synthesis of the transcription factor Fra2.Inhibition of IL-5 reporter constructs by dexamethasone when induced by PMNcAMP, but not PMNCaI, provided a tool for understanding the mechanism. Deletion analysis identified CLEO as the key element of dexamethasone inhibition. Non-inhibition of IL-5 reporter constructs by dexamethasone in a Jurkat cell line, however, showed a possible intermediary factor involved in the inhibition mechanism.

A asma acomete cerca de trezentos milhões de pessoas em todo o mundo. A doença é caracterizada por falta de ar, chiado e compressão no peito, tosse como consequência da hiperresponsividade brônquica e limitação de fluxo aéreo, causadas pela inflamação pulmonar Th2 e eosinofílica. Porém, existem evidências de que a IL-22 e a IL-17 participam da patogênese da asma alérgica. Com intuito de compreender melhor o papel da IL-22 na asma alérgica, utilizamos camundongos deficientes em IL-22 (IL-22KO) comparando-os aos animais Wild Type (WT) expostos ao alérgeno. Animais WT e IL-22KO foram sensibilizados e desafiados com ovalbumina (OVA) e avaliados quanto à inflamação eosinofílica, produção de citocinas, produção de muco, e populações celulares no pulmão. Nossos resultados mostram que a ausência de IL-22 resultou em diminuição da eosinofilia, IL-5 e IL-13 no lavado broncoalveolar, de células CD4+IL-4+ nos linfonodos e diminuição na produção de muco nas vias aéreas. Além disso, os camundongos IL-22KO alérgicos apresentam diminuição na porcentagem e número de células dendríticas CD11c+CD11b+CD103- nos pulmões quando comparados aos respectivo grupo WT. A transferência de células Th17 geradas a partir de animais IL-22KO causou diminuição na eosinofilia em camundongos expostos ao alérgeno quando os mesmos foram comparados aos animais que receberam células Th17 geradas a partir de animais WT. Esse resultado atribui mais à IL-22 do que à IL- 17 papel patogênico na asma alérgica. Outro indício da participação patogênica da IL-22 na asma alérgica é o fato de que o tratamento alérgeno específico, combinado ou não com a terapia livre de alérgeno, induziu redução da eosinofilia, do infiltrado de células dendríticas e diminuição de IL-22 no lavado broncoalveolar. A provável ação da IL-22 é a manutenção da viabilidade e sobrevivência de eosinófilos nos pulmões, fazendo que estes leucócitos continuem auxiliando no recrutamento de células dendríticas responsáveis pela captura e apresentação do alérgeno nos linfonodos, onde haverá a diferenciação de linfócitos de padrão Th2. Essas células podem migrar para os pulmões, gerando aumento na inflamação no local. Em síntese, nosso estudo corrobora o papel proinflamatório da IL-22 na asma alérgica e mostra, de forma inédita, que a transferência de células Th17 produtoras de ambas as citocinas, IL-22 e IL-17, mas não a transferência de células produtoras apenas de IL-17, causa exacerbação da inflamação pulmonar, possivelmente relacionada com o papel da IL-22 em prevenir indiretamente a indução de apoptose nos eosinófilos. / Asthma affects approximately three hundred million people worldwide. The disease is characterized by shortness of breath, wheezing and chest compression, coughing as a result of bronchial hyperresponsiveness and airflow limitation caused by Th2 lung inflammation and eosinophilia. However, there is evidence that IL-22 and IL-17 participate in the pathogenesis of allergic asthma. With the intention to better understand the role of IL-22 in allergic asthma, we used IL-22 deficient mice (IL-22KO) comparing them to wild type animals (WT) exposed to the allergen. Animals WT and IL-22KO were sensitized and challenged with ovalbumin (OVA), and assessed for eosinophilic airway inflammation, cytokine production, mucus production, and cell populations in the lungs. Our results show that the absence of IL-22 resulted in decreased eosinophilia, IL-5 and IL-13 in the bronchoalveolar lavage, CD4 + IL-4 + cells in the lymph nodes and decrease in mucus production in the airways. In addition, allergic IL-22KO mice have decreased percentage and number of dendritic cells CD11c + CD11b + CD103- in lungs when compared to their corresponding WT group. The transfer of Th17 cells generated from IL-22KO animals caused a reduction in eosinophilia in mice exposed to the allergen when they were compared to animals that received Th17 cells generated from WT mice. This result assigns more IL-22 than IL-17 pathogenic role in allergic asthma. Another indication of the pathogenic involvement of IL-22 in allergic asthma is the fact that the specific allergen treatment, combined or not with allergen-free therapy induced a reduction of eosinophilia, the dendritic cell infiltration and decreased IL-22 in bronchoalveolar lavage. The possible action of IL-22 is maintaining the viability and survival of eosinophils in the lungs, making these leukocytes remain helping in the recruitment of dendritic cells responsible for capture and allergen presentation in lymph nodes, causing differentiation in lymphocytes Th2. These cells can migrate to the lungs, resulting in increased inflammation at the site. In summary, our study confirms the proinflammatory role of IL-22 in allergic asthma and shows, in an unprecedented manner, the transfer of producing Th17 cells of both cytokines IL-22 and IL-17, but not the transfer of cells producing only IL-17, cause exacerbation of pulmonary inflammation, possibly related to the role of IL-22 on indirectly prevent induction of apoptosis in eosinophils.

Thesis (M.Sc. (Clinical Tropical Medicine))--Mahidol University, 1983.

A asma acomete cerca de trezentos milhões de pessoas em todo o mundo. A doença é caracterizada por falta de ar, chiado e compressão no peito, tosse como consequência da hiperresponsividade brônquica e limitação de fluxo aéreo, causadas pela inflamação pulmonar Th2 e eosinofílica. Porém, existem evidências de que a IL-22 e a IL-17 participam da patogênese da asma alérgica. Com intuito de compreender melhor o papel da IL-22 na asma alérgica, utilizamos camundongos deficientes em IL-22 (IL-22KO) comparando-os aos animais Wild Type (WT) expostos ao alérgeno. Animais WT e IL-22KO foram sensibilizados e desafiados com ovalbumina (OVA) e avaliados quanto à inflamação eosinofílica, produção de citocinas, produção de muco, e populações celulares no pulmão. Nossos resultados mostram que a ausência de IL-22 resultou em diminuição da eosinofilia, IL-5 e IL-13 no lavado broncoalveolar, de células CD4+IL-4+ nos linfonodos e diminuição na produção de muco nas vias aéreas. Além disso, os camundongos IL-22KO alérgicos apresentam diminuição na porcentagem e número de células dendríticas CD11c+CD11b+CD103- nos pulmões quando comparados aos respectivo grupo WT. A transferência de células Th17 geradas a partir de animais IL-22KO causou diminuição na eosinofilia em camundongos expostos ao alérgeno quando os mesmos foram comparados aos animais que receberam células Th17 geradas a partir de animais WT. Esse resultado atribui mais à IL-22 do que à IL- 17 papel patogênico na asma alérgica. Outro indício da participação patogênica da IL-22 na asma alérgica é o fato de que o tratamento alérgeno específico, combinado ou não com a terapia livre de alérgeno, induziu redução da eosinofilia, do infiltrado de células dendríticas e diminuição de IL-22 no lavado broncoalveolar. A provável ação da IL-22 é a manutenção da viabilidade e sobrevivência de eosinófilos nos pulmões, fazendo que estes leucócitos continuem auxiliando no recrutamento de células dendríticas responsáveis pela captura e apresentação do alérgeno nos linfonodos, onde haverá a diferenciação de linfócitos de padrão Th2. Essas células podem migrar para os pulmões, gerando aumento na inflamação no local. Em síntese, nosso estudo corrobora o papel proinflamatório da IL-22 na asma alérgica e mostra, de forma inédita, que a transferência de células Th17 produtoras de ambas as citocinas, IL-22 e IL-17, mas não a transferência de células produtoras apenas de IL-17, causa exacerbação da inflamação pulmonar, possivelmente relacionada com o papel da IL-22 em prevenir indiretamente a indução de apoptose nos eosinófilos. / Asthma affects approximately three hundred million people worldwide. The disease is characterized by shortness of breath, wheezing and chest compression, coughing as a result of bronchial hyperresponsiveness and airflow limitation caused by Th2 lung inflammation and eosinophilia. However, there is evidence that IL-22 and IL-17 participate in the pathogenesis of allergic asthma. With the intention to better understand the role of IL-22 in allergic asthma, we used IL-22 deficient mice (IL-22KO) comparing them to wild type animals (WT) exposed to the allergen. Animals WT and IL-22KO were sensitized and challenged with ovalbumin (OVA), and assessed for eosinophilic airway inflammation, cytokine production, mucus production, and cell populations in the lungs. Our results show that the absence of IL-22 resulted in decreased eosinophilia, IL-5 and IL-13 in the bronchoalveolar lavage, CD4 + IL-4 + cells in the lymph nodes and decrease in mucus production in the airways. In addition, allergic IL-22KO mice have decreased percentage and number of dendritic cells CD11c + CD11b + CD103- in lungs when compared to their corresponding WT group. The transfer of Th17 cells generated from IL-22KO animals caused a reduction in eosinophilia in mice exposed to the allergen when they were compared to animals that received Th17 cells generated from WT mice. This result assigns more IL-22 than IL-17 pathogenic role in allergic asthma. Another indication of the pathogenic involvement of IL-22 in allergic asthma is the fact that the specific allergen treatment, combined or not with allergen-free therapy induced a reduction of eosinophilia, the dendritic cell infiltration and decreased IL-22 in bronchoalveolar lavage. The possible action of IL-22 is maintaining the viability and survival of eosinophils in the lungs, making these leukocytes remain helping in the recruitment of dendritic cells responsible for capture and allergen presentation in lymph nodes, causing differentiation in lymphocytes Th2. These cells can migrate to the lungs, resulting in increased inflammation at the site. In summary, our study confirms the proinflammatory role of IL-22 in allergic asthma and shows, in an unprecedented manner, the transfer of producing Th17 cells of both cytokines IL-22 and IL-17, but not the transfer of cells producing only IL-17, cause exacerbation of pulmonary inflammation, possibly related to the role of IL-22 on indirectly prevent induction of apoptosis in eosinophils.

Orientador: Edson Antunes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-04T02:40:18Z (GMT). No. of bitstreams: 1 Costa_GislaineGomesda_M.pdf: 3654162 bytes, checksum: ae2e21b58ce18e882aab17b0529a6576 (MD5) Previous issue date: 2004 / Resumo: Neste estudo, investigamos se a IL-5, a eotaxina e a dexametasona modulam a migração e adesão de eosinófilos obtidos de indivíduos sadios e de pacientes com rinite alérgica. O ensaio de quimiotaxia e de adesão foi realizado com eosinófilos de sangue periférico usando-se sistema imunomagnético de separação celular. Para os ensaios de quimiotaxia, foram utilizadas placas ChemoTx-5, e para os ensaios de adesão, placas de adesão recobertas com fibronectina. Em ambos os ensaios, a medida da absorbância (490 nM) da peroxidase eosinofílica foi utilizada como índice de eosinófilos migrados ou aderidos. O PAF (10~ M) induziu quimiotaxia de mesma magnitude em eosinófilos de indivíduos sadios e de pacientes com rinite. A IL-5 (0,25 nglml) aumentou significativamente a quimiotaxia de eosinófilos induzida pelo PAF; porém, o aumento observado em eosinófilos de pacientes com rinite alérgica foi 65% maior (p<0,001) do que de indivíduos sadios. A eotaxina (100 nglml) não alterou a resposta quimiotáxica do PAF em nenhum dos grupos estudados. A dexametasona (100 J.1g/ml)reduziu significativamente a quimiotaxia, tanto no grupo de indivíduos sadios, como no de pacientes com rinite alérgica. A IL-5 (0,25 ng/ml) induziu resposta quimiotáxica significativamente maior em eosinófilos de pacientes com rinite, em comparação com eosinófilos de indivíduos sadios. A resposta quimiotáxica à IL-5 não foi modificada pela eotaxina (100 ng/ml) em eosinófilos de indivíduos sadios, mas foi marcantemente reduzida em eosinófilos de pacientes com rinite alérgica. A eotaxina (100 nglml) induziu resposta quimiotáxica significativamente maior em eosinófilos de pacientes com rinite, em comparação com eosinófilos de indivíduos sadios. A resposta quimiotáxica à eotaxina foi potencializada pela IL-5 (100 ng/ml)em eosinófilos de indivíduos sadios e de pacientes com rinite alérgica. Entretanto, o aumento observado nos eosinófilos de pacientes com nnite alérgica foi significativamente maior do que de indivíduos sadios. Em placas recobertas com fibronectina (10 J.1g1m,l) ligante oposto da molécula de adesão VLA-4, estudamos a adesão dos eosinófilos. A adesão espontânea foi maior com eosinófilos de pacientes com rinitealérgica do que de indivíduos sadios. A incubação dos eosinófilos com eotaxina (100 nglml) ou IL-5 (0,25 ng/ml) não modificou a adesão dos eosinófilos em nenhum dos grupos estudados. A incubação com dexametasona (100 J.1g1ml) reduziu significativamente a adesão celular em ambos os grupos experimentais. Nossos resultados mostram que eosinófilos de pacientes com rinite alérgica estão pré-ativados. Isto pode ser devido à exposição na circulação à IL-5, que leva ao aumento da expressão elou função da molécula de adesão VLA-4 e, conseqüentemente,de sua migração / Abstract: In this study, we tested whether IL-5, eotaxin and dexamethasone modulate the adhesion and migration of eosinophils obtained trom allergic rhinitis subjects, in comparison with healty individuais. The chemotaxis and adhesion assays were performed with eosinophils isolated from peripheral blood using an imunomagnetic cell separator. ChemoTx-5 plates were used for the chemotaxis assays, whereas fibronectin-coated plates were used for the adhesion assays. For both assays, measurement of eosinophil peroxidase activity was used as marker for migrated or adhered eosinophils. Platelet-activated factor (PAF; 10-8 M) induced a significant eosinophil chemotaxis in both studied groups. Interleukin-5 (IL-5, 0.25 nglml) significantly increased the PAF-induced chemotaxis in eosinophils trom both healthy individuais and rhinitis subjects. However, the increase in rhinitis subjects eosinophils was 65% higher (p<0.001) compared with healthy individuais eosinophils. Eotaxin (100 ng/ml) did not alter the PAF-induced eosinophil chemotaxis in either groups studied. Dexamethasone (100 Ilg/ml) significantly reduced PAF-induced chemotaxis in cells trom both groups. Interleukin-5 (0.25 nglm!) induced a higher chemotactic response in eosinophils trom rhinitis subjects compared with healthy individuais. Eotaxin (100 ng/ml) had no effect on IL-5-induced eosinophil chemotaxis in healthy individuais, but prevented the increase in eosinophil chemotaxis induced by IL-5 in rhinitis subjects. Eotaxin (100 ng/ml) induced a higher chemotactic response in eosinophils trom rhinitis subjects compared with healthy individuais. Eotaxin-induced eosinophil chemotaxis was significantly enhanced by IL-5 (0.25 nglml) in both group studied, but this enhancement was higher in eosinophils trom rhinitis subjects. In plated coated with fibronectin (an opposite ligand for VLA-4) we studied the eosinophil adhesion. The basal (spontaneous) cell adhesion was siginificantly higher (p<0.05) using eosinophils from rhinitis subjects compared with those trom healthy individuais. However, the pattem of cell adhesion in both groups was not significantlyaffectedby eotaxin (100 ng/ml) or IL-5 (0.25 nglm!). Dexamethasone (100 Ilg/ml) significantly reduced the eosinophil adhesion in cells from both studied groups. Ours results indicate that eosinophils trom rhinitissubjects are found primed, and that can be due to previous exposition to IL-5 while in peripheral blood. It is likelythat IL-5 increases the expression andlor function01adhesion molecule VLA- 4 in eosinophils leading consequently to an enhanced cell chemotaxis / Mestrado / Farmacologia / Mestre em Farmacologia

Eosinophilia is not an uncommon finding on a routine complete blood count (CBC) during a primary care visit. The differential diagnosis is varied including allergic/atopic disease, drug reaction, infection, inflammatory conditions, and malignancy. An 80-year-old male was incidentally found to have leukocytosis on routine labs. White blood cell (WBC) was 27.5 K/ul with eosinophilia 4.3 K/ul (normal range 0-0.6 Kul) and Hemoglobin/Platelet counts were normal. Patient was asymptomatic. Denied history of medication change or allergy. Chest X-Ray (CXR) followed by Computed tomography (CT) showed 5 cm pulmonary mass with mediastinal lymphadenopathy. Patient developed progressively enlarging left neck mass, hoarseness, weight loss and decreased appetite in the next 3 weeks. WBC increased steeply to 65 K/ul with eosinophil count - 18.5 K/ul. CT neck revealed a large heterogeneous mass of the thyroid extending to the trachea, esophagus, and mediastinum. Patient decided not to proceed with further diagnostic workup and management given his age and comorbidities. Eosinophilia can be asymptomatic or present with nonspecific symptoms like cough, fatigue, skin rash or neuropathy. Eosinophilia work up starts with a comprehensive history detailing travel history, exposure to well water/spring water, analysis of past medical history to include asthma, atopy and especially medication history. Physical exam with attention to atopy/eczema and skin rash is vital. Work up may include a CBC, peripheral blood smear, stool test (for ova and parasite), IgE/tryptase levels and evaluation for occult malignancy (CXR is an ideal first step). Further testing with Bone marrow biopsy and CT scans is a consideration if a clear diagnosis is not achieved. Life-threatening complications of untreated hyper-eosinophilia include thromboembolism, endomyocardial fibrosis, cognitive disturbances, and respiratory failure. Incidence of eosinophilia is 1% in malignant tumors. Malignancy encompasses hematological cancers (acute leukemia, chronic myeloid leukemia, systemic mastocytosis, lymphoid neoplasms) and solid tumors (lung, thyroid, breast and gastrointestinal tract cancers). Eosinophilia suggests advanced disease in solid tumors and portends poor prognosis. Paraneoplastic eosinophilia has been reported in thyroid cancer (sclerosing muco-epidermoid) and lung cancer (squamous and adenocarcinoma). Pathophysiology of eosinophilia in solid tumors is related to bone marrow stimulation through cytokines (interleukin-5, granulocyte-macrophage colony-stimulating factor, and interleukin-2). Primary eosinophilia responds to steroids and hydroxyurea. Treating the underlying malignancy is the cornerstone of paraneoplastic eosinophilia management. We present a case of extreme progressive eosinophilia secondary to a malignancy which would be of interest to the primary care clinician.

Hyper eosinophilia with cardiomyopathy as manifestation of Churg Strauss syndrome Hakam Khazrik MD1, Purva Sharma MD1 Division of Hematology/Oncology, Dept of Internal Medicine, East Tennessee State University. Eosinophilia (≥500 eosinophils/micro-L) and hyper eosinophilia (≥1500 eosinophils/micro-L) could be caused by many conditions including allergic, infectious, inflammatory and neoplastic disorders. Patient may present with severe organ involvement require hospitalization and urgent intervention. A 39-year-old female with history of asthma, nasal polyps presented with worsening dyspnea, lower extremity edema, acute left heart failure and non-ST elevation myocardial infarction with significant troponin elevation (31 ng/ml). Cardiac catheterization revealed no stenosis, echocardiogram showed severely reduced ejection fraction 20%. She was managed medically with presumptive diagnosis of viral myocarditis. One month later she represented with similar symptoms associated with mild facial malar rash and worsening peripheral eosinophilia (absolute count 6400cells/micro-L), leukocytosis (WBC 11k/ul norma differential except eosinophilia mild anemia Hg: 10g/dl, normal platelet(304k/ul), normal renal and liver functions, mild elevated tryptase 16. CT chest revealed bilateral hilar lymphadenopathy with no pulmonary infiltrate. Parasite, fungal,, tuberculosis, HIV, hepatitis infections were ruled out. Bone marrow biopsy revealed hypercellular marrow for age, mild increased marrow eosinophilic precursor, normal cytogenetics, FISH studies for MDS, eosinophilia, and BCR-ABL as well as molecular MPN panel were unremarkable. No lymphoproliferative disorder or increased blasts noted. Subcarinal lymph node biopsy with normal lymph node tissue. Extensive rheumatological workup was unremarkable except for elevated rheumatoid factor, ESR, CRP, anti-myeloperoxidase and anti-protease- 3. Eosinophilic granulomatosis with polyangiitis, (EGPA)was diagnosed. Patient started on long taper prednisone with improvement in her symptoms and her eosinophilia. Given severe disease with cardiac involvement she was started on cyclophosphamide to improve her prognosis. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss), is multisystem disorder characterized by chronic rhinosinusitis, asthma and prominent peripheral blood eosinophilia. Asthma is the cardinal feature. Skin and neurological involvement is usually common but cardiac involvement is one of the more serious manifestations of EGPA accounting for approximately one-half of deaths attributable to EGPA. Two sets of diagnostic criteria are commonly used: the American College of Rheumatology (ACR) criteria and the Lanham criteria. Main diseases to consider in the differential diagnosis of EGPA are aspirin-exacerbated respiratory disease, the eosinophilic pneumonias, allergic bronchopulmonary aspergillosis, hyper eosinophilic syndrome, granulomatosis with polyangiitis and microscopic polyangiitis.

No description available.