Interventions for cutaneous disease in systemic lupus erythematosus.

BACKGROUND: Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many interventions are used to treat SLE with varying efficacy, risks, and benefits. OBJECTIVES: To assess the effects of interventions for cutaneous disease in SLE. SEARCH METHODS: We searched the following databases up to June 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, Wiley Interscience Online Library, and Biblioteca Virtual em Saude (Virtual Health Library). We updated our search in September 2020, but these results have not yet been fully incorporated. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions for cutaneous disease in SLE compared with placebo, another intervention, no treatment, or different doses of the same intervention. We did not evaluate trials of cutaneous lupus in people without a diagnosis of SLE. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were complete and partial clinical response. Secondary outcomes included reduction (or change) in number of clinical flares; and severe and minor adverse events. We used GRADE to assess the quality of evidence. MAIN RESULTS: Sixty-one RCTs, involving 11,232 participants, reported 43 different interventions. Trials predominantly included women from outpatient clinics; the mean age range of participants was 20 to 40 years. Twenty-five studies reported baseline severity, and 22 studies included participants with moderate to severe cutaneous lupus erythematosus (CLE); duration of CLE was not well reported. Studies were conducted mainly in multi-centre settings. Most often treatment duration was 12 months. Risk of bias was highest for the domain of reporting bias, followed by performance/detection bias. We identified too few studies for meta-analysis for most comparisons. We limited this abstract to main comparisons (all administered orally) and outcomes. We did not identify clinical trials of other commonly used treatments, such as topical corticosteroids, that reported complete or partial clinical response or numbers of clinical flares. Complete clinical response Studies comparing oral hydroxychloroquine against placebo did not report complete clinical response. Chloroquine may increase complete clinical response at 12 months' follow-up compared with placebo (absence of skin lesions) (risk ratio (RR) 1.57, 95% confidence interval (CI) 0.95 to 2.61; 1 study, 24 participants; low-quality evidence). There may be little to no difference between methotrexate and chloroquine in complete clinical response (skin rash resolution) at 6 months' follow-up (RR 1.13, 95% CI 0.84 to 1.50; 1 study, 25 participants; low-quality evidence). Methotrexate may be superior to placebo with regard to complete clinical response (absence of malar/discoid rash) at 6 months' follow-up (RR 3.57, 95% CI 1.63 to 7.84; 1 study, 41 participants; low-quality evidence). At 12 months' follow-up, there may be little to no difference between azathioprine and ciclosporin in complete clinical response (malar rash resolution) (RR 0.83, 95% CI 0.46 to 1.52; 1 study, 89 participants; low-quality evidence). Partial clinical response Partial clinical response was reported for only one key comparison: hydroxychloroquine may increase partial clinical response at 12 months compared to placebo, but the 95% CI indicates that hydroxychloroquine may make no difference or may decrease response (RR 7.00, 95% CI 0.41 to 120.16; 20 pregnant participants, 1 trial; low-quality evidence). Clinical flares Clinical flares were reported for only two key comparisons: hydroxychloroquine is probably superior to placebo at 6 months' follow-up for reducing clinical flares (RR 0.49, 95% CI 0.28 to 0.89; 1 study, 47 participants; moderate-quality evidence). At 12 months' follow-up, there may be no difference between methotrexate and placebo, but the 95% CI indicates there may be more or fewer flares with methotrexate (RR 0.77, 95% CI 0.32 to 1.83; 1 study, 86 participants; moderate-quality evidence). Adverse events Data for adverse events were limited and were inconsistently reported, but hydroxychloroquine, chloroquine, and methotrexate have well-documented adverse effects including gastrointestinal symptoms, liver problems, and retinopathy for hydroxychloroquine and chloroquine and teratogenicity during pregnancy for methotrexate. AUTHORS' CONCLUSIONS: Evidence supports the commonly-used treatment hydroxychloroquine, and there is also evidence supporting chloroquine and methotrexate for treating cutaneous disease in SLE. Evidence is limited due to the small number of studies reporting key outcomes. Evidence for most key outcomes was low or moderate quality, meaning findings should be interpreted with caution. Head-to-head intervention trials designed to detect differences in efficacy between treatments for specific CLE subtypes are needed. Thirteen further trials are awaiting classification and have not yet been incorporated in this review; they may alter the review conclusions.

Immunotherapies in dermatologic disorders.

Treatment modalities and therapeutic response experience support the use of immunotherapy in the treatment of many diseases in all fields of medicine. The aim of this article is to conduct and present a review of literature on the use of immunotherapy in the treatment of skin diseases analyzing scientific literature available up to January 2012. Studies that presented evidence-based data were selected. The article discusses how blocking or reverting the effect of a specific immunologic disequilibrium can treat dermatoses and intends to transfer a large amount of immunotherapy knowledge into a historical perspective for physicians naive to immunotherapy practices.

Impact of the number of dermatologists on dermatology biomedical research: a Canadian study.

BACKGROUND: Fewer dermatologists than other clinical specialists are entering and being retained as physicians in the Canadian medical workforce. Studies suggest that dermatologist numbers may influence skin disease outcomes. No study has questioned whether the number of clinical dermatologists can influence academic productivity. OBJECTIVE: To quantify the correlation of the number of dermatologists with biomedical scientific production in this field from 1996 to 2008 in Canada. METHODS: Canadian dermatology biomedical scientific production from SCImago Journal & Country Rank (SJR) were merged with Canadian Medical Association (CMA) dermatologist demographic data. Linear regression analyses were used to model the relationships. RESULTS: The low growth of dermatologist numbers by 8.16% in Canada from 1996 to 2008 correlates with a small increase in articles by 7.59% published in this subject area during this period. This has reduced the scientific importance of Canadian dermatology in the world. CONCLUSION: The number of dermatologists was a significant predictor of biomedical research production in the field of dermatology. This suggests that specialist availability may be one factor influencing dermatology research and publications.

Suppression of histamine- and allergen-induced skin reactions: comparison of first- and second-generation antihistamines.

BACKGROUND: Nonsedating antihistamines (nsAHs) are recommended as first-line therapeutics for the treatment of mast cell-driven disorders, including allergic rhinitis and urticaria. However, their superiority over first-generation AHs (fgAHs) has recently been called into question, mainly because of the lack of supporting head-to-head therapeutic studies. OBJECTIVE: To compare the effects of 3 modem nsAHs with those of the fgAH hydroxyzine on histamine- and allergen-induced skin reactions in a controlled, double-blind, clinical trial. METHODS: Skin prick tests with histamine and Dermatophagoides pteronyssinus extract were performed before and 4 hours after treatment with hydroxyzine, 25 mg; desloratadine, 5 mg; epinastine, 20 mg; fexofenadine, 120 mg; or placebo. Wheal and erythema development was evaluated by digital photography and planimetric analyses. RESULTS: The nsAHs prevented the development of positive reactions to histamine in only 10% to 20% of all individuals tested (n = 75). In contrast, more than 50% of all hydroxyzine-treated individuals showed negative test reactions to histamine (ie, wheals <7 mm2 in area or <3 mm in diameter). Similar differences, although less pronounced, were detected when comparing the effects of nsAHs with hydroxyzine on D pteronyssinus prick testing in a limited number of D pteronyssinus-sensitized individuals. CONCLUSIONS: These results indicate that hydroxyzine is more effective than nsAHs when given as recommended in suppressing histamine-induced or allergic skin reactions. Our results suggest that higher doses of nsAHs than those currently recommended are required for the treatment of skin responses to obtain antihistaminic and antiallergic effects that are equivalent to those of fgAHs.

Long-term safety of biologics in dermatology.

The use of biologics in dermatology has increased rapidly. Although most are relatively safe when correctly used and monitored, there are known side effects and adverse events that occur. Selection of patients should be done on a case-by-case basis. Severity of disease, comorbidity profile, drug profile, and cost-effectiveness should be all taken into consideration while deciding to start and/or maintain one of these therapies. Dermatologists should be aware of the benefits and limitations of this class of drugs, as well as the appropriate monitoring. The authors propose a concise overview of the safety profiles of some of the biologics currently used in the dermatologic field.

Avaliação da intensidade das rugas periorbitais por processamento digital de imagens: um estudo de validação / Periorbital wrinkle severity evaluation using digital image processing: a validation study

Introdução: Dermatologistas podem avaliar a qualidade da pele de um paciente através de suas rugas faciais. Existem diversos métodos descritos para quantifi car as microelevações e rugas da pele. Objetivo: O objetivo deste estudo é utilizar a tecnologia de processamento de imagem para avaliar a área das rugas e sua correlação com a avaliação do dermatologista. Material e Métodos: Cento e setenta e um voluntários selecionados aleatoriamente, com idades variando de 18 a 69 anos, de ambos os sexos, com pele tipos II-IV de Fitzpatrick e I-IV de Glogau, participaram deste estudo. Fotografi as digitais foram tiradas sob duas condições diferentes: com as rugas relaxadas (RR) ou contraídas (RC). Foram tiradas pelo menos seis fotografi as para determinar a reprodutibilidade de cada método. Seis dermatologistas avaliaram as fotografi as e marcaram as rugas dos pacientes com uma caneta digital. Determinou-se a intensidade das rugas por três diferentes métodos de processamento de imagens. A avaliação quantitativa da intensidade das pregas cutâneas e a consistência inter e intramétodo foram estabelecidas e comparadas à avaliação manual. Resultados: A variabilidade dos dermatologistas foi de 61,49%. A concordância intratestes variou de 4,4 a 31%. O método do gradiente obteve os melhores resultados e detectava as condições das rugas (p < 0,001), tendo apresentado também uma correlação positiva com a avaliação manual. Conclusões: As rugas periorbitais foram identifi cadas. Os dermatologistas demonstraram precisão interna, mas baixa exatidão. O processamento digital do operador de Sobel é um instrumento válido e confi ável para a avaliação quantitativa de rugas.

Introduction: Dermatologists get an idea of how old a patient is by looking face's wrinkles. Different methods exist to quantify skin microrelief and wrinkles. Objective: To use imaging process technology to assess the wrinkle area and its interrelation with dermatologist determination. Material and methods: One hundred seventy-one volunteers, randomly selected, aged 18­69 years, both gender, Fitzpatrick skin type II­IV, with Glocau I­IV were selected. Digital photography was obtained. Two different conditions, relaxed or contract wrinkle condition (CWC), and at least six repeated pictures for repeatability capacity of each method. Six participating dermatologists evaluated the pictures and ascertained patients' wrinkle using a digital pen. Wrinkle intensity was done by three different image processing methods. Quantitative assessment of facial skin folds intensity, and inter- plus intra-method consistency were determined and compared to manual evaluation. Results: Dermatologists variability was 61.49%. Intra-tests agreement varied from 4.4 to 31%. The gradient method had the best results and could detect the wrinkle conditions (p < 0.001). Also, this method had a positive correlation with the manual assessment. Conclusions: Periorbital wrinkles could be determined. Dermatologists had internal precision but low accuracy. Sobel Operator digital processing is a valid and reliable instrument for quantitative wrinkle assessment.

CARD15 and IL23R influences Crohn's disease susceptibility but not disease phenotype in a Brazilian population.

BACKGROUND: Although many genetic variants are identified in association with Crohn's disease (CD), CARD15, IL23R, and ATG16L1 association with CD have been firmly confirmed in Caucasians of European ancestry. The prevalence of CD is rapidly rising in Brazil, where European ancestry is firmly admixed with natives and Africans, resulting in a heterogeneous population. We investigated the contribution of CARD15, IL23R, and ATG16L1 with CD risk in a heterogeneous Brazilian population. METHODS: Genotyping for CARD15 (R702W, G908R, 3020insC), IL23R (rs1004819, rs7517847, rs11209026, rs10889677, rs1495965), and ATG16L1 (rs2241880) was performed in 187 children and adults with CD and 255 healthy ethnically matched controls. Clinical records were systematically reviewed and detailed phenotypic information was obtained. RESULTS: At least 1 CARD15 risk allele was present in 30% of the CD patients compared with 10% of controls. Variants of CARD15 (3020insC and R702W) and IL23R (rs1004819, rs11209026, and rs1088967) were associated with CD. However, no genotype-phenotype correlations were found among the Brazilian CD population with CARD15 or IL23R variants. No significant association was achieved with ATG16L1. CONCLUSIONS: CARD15 and IL23R confer susceptibility to CD in the Brazilian population. However, the presence of these variants did not influence disease phenotype. Further research should be focused on larger sample sizes with population admixture analysis to better understand the risks and genotype-phenotype correlation in populations like Brazil where the prevalence of CD is rapidly rising.

Cinética da reação cutânea induzida por puntura / Kinetic of skin prick test reaction using digital photography

Objetivo: Demonstrar e comparar a cinética de três sinais inflamatórios da reação cutânea in vivo: eritema, pápula e temperatura. Métodos: Estudo experimental. Foi determinada a velocidade das variáveis da reação cutânea induzida por histamina e Dermatophagoides pteronyssinus na face anterior do antebraço de voluntários, aos O, 3, 5, 10, 15 e 20 minutos. Uso de antihistamínico foi critério de exclusão. O tamanho da pápula, e o tamanho e a intensidade do eritema foram determinados pela análise das imagens em fotografia digital. Filmou-se o local do teste cutâneo durante 20 minutos com câmera infravermelha de alta sensibilidade, em ambiente a 19°C, sem corrente de ar. Os dados foram analisados em software específico. Todos os dados foram transformados por um fator de unidade no 10 minuto de cada grandeza. Determinou-se em cada .ponto a tangente da curva de intensidade unitária e dividiu-se cada resultado pelo tempo entre cada ponto específico. Resultados da velocidade foram expressos em unidade:!: erro padrão. Resultados: Não houve diferença na cinética da reação entre os desafios. Nos primeiros três minutos a intensidade do eritema atingiu velocidade máxima, com diferença significativa em relação à pápula e à temperatura. A pápula obteve velocidade maior entre o 50 e o 100 minuto em relação ao eritema. Conclusões: Termometria cutânea e fotografia digital são métodos objetivos de leitura do teste cutâneo por puntura; incorporam novas variáveis nos testes cutâneos e no diagnóstico de doenças alérgicas mediadas por IgE e determinam a cinética do desenvolvimento da reação cutânea refletindo a reação tríplice de Lewis

Effect of Lutzomyia longipalpis salivary gland extracts on leukocyte migration induced by Leishmania major.

The mechanism by which the salivary gland lysate (SGL) of Lutzomyia longipalpis enables Leishmania infection remains under investigation. One possibility is that saliva promotes cellular recruitment leading to development of skin lesions. In this study, we investigated leukocyte recruitment induced by L. major, L. major + SGL, or SGL alone into the peritoneal cavity of BALB/c mice. The administration of L. major with or without SGL induced neutrophil migration six hours after infection. Interestingly, after seven days, the BALB/c mice still had eosinophils and mononuclear cells in their peritoneal cavities. Flow cytometric analysis showed an increase in the CD4(+) CD45RB(low) T cell subset (effector or memory cells) compared with the CD4(+) CD45RB(high) subset (naive cells). Moreover, the co-injection of L. major with SGL enhanced production of interleukin-10. These results suggest that SGL can facilitate Leishmania infection by modulating leukocyte recruitment and Th2 cytokine production at the inflammatory focus.

Different inflammatory mediators induce inflammation and pain after application of liquid nitrogen to the skin.

The application of liquid nitrogen to the skin induces inflammation and pain. However, there is little data on the role of inflammatory mediators in the production of these symptoms. We have developed an experimental model to study some aspects of the inflammatory response and its mediators following the application of cold. We have applied liquid nitrogen jets to subcutaneous air pouches in the dorsal skin of rats to study the kinetics of the migration of inflammatory cells; also to the ear for histopathological analysis and on the paws for edema and pain. Inflammatory mediators were identified by pharmacological means. The results showed that the cellular inflammatory response was characterized by persistent cell migration, mainly of granulocytes. Histopathology of the ears confirmed these findings. Histamine and sympathomimetic mediators were mainly responsible for the resultant swelling. However, the hypernociception that resulted involved other mediators including IL-1 and eicosanoids. These data suggest that interference with the release of inflammatory mediators might reduce the side effects of cryosurgery and prevent hyperalgesia and inflammation at the site of application of cold.

Aplicações terapêuticas dos anticorpos monoclonais / Monoclonal antibodies therapeutic applications

Objetivo: Conduzir e apresentar revisão da literatura sobre a produção e uso clínico dos anticorpos monoclonais empregados no tratamento de doenças. Métodos: Revisão sistemática de trabalhos científicos relevantesde banco de dados eletrônicos até janeiro de 2006. Foram selecionados artigos que abordassem o tema anticorpos monoclonais nos seguintes aspectos: definição, mecanismo de ação, aplicação terapêutica e efeitos colaterais. Resultados: Muitos anticorpos monoclonais estão licenciados para uso clínico e outros em desenvolvimento clínico avançado. As terapias baseadas neste grupo de biológicos apresentam vantagens e desvantagens quando comparadas a terapias convencionais. Versatilidade, especificidade, e ações não reproduzidas pelas drogas tradicionais são as vantagens desses bioterápicos. Entretanto, o alto custo reduz seu uso em larga escala. Conclusão: Nos últimos anos anticorpos monoclonais passaram a ser uma terapia de primeira linha para uma variedade de condições que incluem infecções virais, distúrbios inflamatórios e neoplasias, além do mais, terapias baseadas em anticorposn podem ser desenvolvidas com sucesso para uso em situações clínicas onde nenhuma terapia efetiva esteja disponível. Médicos de diversas especialidades precisarão de mais experiências clínicas para usarem rotineiramente esses compostose entenderem seus mecanismos básicos de ação.

Associação entre sensibilidade aos antiinflamatórios não esteroidais e sensibilização ao ácaro de estocagem G. domesticus / Association between non-steroidal anti-inflammatory sensibility and sensitivity to G. domesticus a storage mite

Objetivo: Embora se saiba que a sensibilização aos ácarosde estocagem está associada à sensibilidade aos antiinflamatórios não esteroidais (AINE), não existem dados sólidos estabelecendo que a correlação inversa exista. Nós realizamos um ensaio de observação transversal para determinar se sensibilidade a AINE pode ser prevista pela sensibilidade a ácaros de estocagem.Métodos: Cem pacientes voluntários, consistindo de pessoas com idade entre 9 e 69 anos que procuravam o ambulatório de alergia, foram selecionados baseados no diagnóstico de sensibilidade a AINE. Teste de puntura para determinar a sensibilidade aos diferentes extratos alergênicos foram realizados e uma medida à cega do tamanho da pápula obtido. Uma entrevista foi também feita para estabelecer a presença de sensibilidade ao AINE. Mediu-se a associação entre a sensibilidade a cada extrato alergênico e o diagnóstico de sensibilidade a AINE. Regressão logística foi usada para determinar o modelo que mais predizia a sensibilidade a AINE usando cada ou a combinação do resultado dos extratos. A associação foi considerada estatisticamente importante se o valor de p fosse menor que 0.05. Resultados: Os testes para os extratos de G. domesticus (p=0.0084, qui-quadrado), B. kulagini (p=0.0407, qui-quadrado), D. farinae (p=0.026, qui-quadrado), A. ovatus (p=0.0386,qui-quadrado) e T. putrescentiae (p=0.0428, qui-quadrado)determinaram associação significativa com AINE, porém odiagnóstico de atopia foi um confundidor para todos os extratos exceto um. O extrato alergênico do G. domesticus foi único na sua capacidade de prever o diagnóstico de sensibilidade a AINE (SqrtMS = 14,097 p<0,05 por regressão logística). Conclusões: O diagnóstico de sensibilidade a AINE pode ser previsto pelo teste de puntura usando um extrato alergênico de G. domesticus e um valor elevado para um questionário de entrevista em condições baseadas em um hospital.(au)

Adjuvantes de vacinas: possibilidades de uso em seres humanos ou animais / Vacine adjuvants: possibilities for use in humans or animals

Objetivo: Rever de forma sistemática as substânciasadjuvantes mais estudadas, utilizadas e as novassubstâncias; com o intuito de atualizar os conceitos desua ação por atuarem, juntamente com o antígeno, nosistema imunológico e seu futuro uso em vacinas humanasou animais. Métodos: Foi realizada revisão sistemática em livros e da literatura publicada no Medline® a partir do ano de 1969. Foram selecionados artigos que abordassemo tema “adjuvantes” nos seguintes aspectos: Respostainflamatória, resposta imune celular, resposta imune humoral, seqüelas, proteção. Resultados: Foram selecionados artigos originais ou capítulos de livros abordando este tema. Observou-se haver diferenças na capacidade de indução inflamatória entre os diferentes adjuvantes. Estas diferenças podem resultar em padrões de resposta imune celular e humoral diferenciados, de acordo com a célula mais estimulada. Assim, adjuvantes indutores de migração predominantemente mononuclear parecem facilitar respostas do padrão celular e humoral. Respostas mais neutrofílicas podem resultar em maiores efeitos colaterais locais e/ou sistêmicos e também podemser associados à redução da disponibilidade antigênicapara o sistema imunológico. Conclusões: O sistema imunológico animal ou humano pode se comportar de maneira diferenciada frente aos diferentes tipos de substâncias adjuvantes. Os mesmos mecanismos usados pelo organismo para proteção contra infecções podem, em situações particulares, serem causadores de doenças, por isso a importância do estudo individual de cada adjuvante a ser utilizado em cada situação e a necessidade de se encontrar uma substância que seja efetiva frente a grande número de antígenos e que diminua sobremaneira possíveis seqüelas.

Parâmetros inflamatórios do teste cutâneo por puntura determinados por fotografia digital e termometria cutânea / Evaluation of skin prick test using digital photography and skin infrared thermography

Objetivo: Empregar novos recursos na leitura doprick test pela fotografia digital e variação da temperatura através de câmera infravermelha.Método: Estudo experimental. Determinação daárea da pápula e intensidade do eritema por histaminae Dermatophagoides pteronyssinus por puntura, facevolar do antebraço de 93 voluntários de diferentes fototipos. Câmera digital fixada e fotografias à mesmadistância, 0, 3, 5, 10, 15 e 20min. Círculo como referência de área próximo ao teste. Fotografias armazenadas e dados determinados pelo Adobe Photoshop.Área da pápula determinada por filtros. Intensidade eluminosidade das cores comparadas com área normal.Leitura feita por medida do diâmetro médio e pelareação transferida à fita adesiva e analisada por computador. Filmagem do local do teste com câmerainfravermelha. Resultados: Aumento na área da pápula por histamina e Dermatophagoides pteronyssinus, sem diferençaentre as curvas (p=0,73). Ponto máximo de proximidadeentre as curvas no 10 min, com área média da pápula de 27,47mm² e 30,7mm², respectivamente. Cor vermelha variou significativamente quando comparada à pele normal. Intensidade do vermelho variou de 0,38 ± 2,57 a 8,26 ± 3,48 (p0.001). Cor verde reduziu ao mesmo tempo. Aumento na temperatura de 2± C ao 20 min de observação, com curvas semelhantes àquelas da área da pápula.Conclusão: Fotografia digital permite medida objetivada área da pápula e intensidade do eritema. Estemétodo poderá ser usado para avaliar intensidade deinflamação cutânea. Intensidade do eritema e aumentoda temperatura parecem ser diretamente proporcionaisao aumento da área da pápula.

TNF-alpha mediates the induction of nitric oxide synthase in macrophages but not in neutrophils in experimental cutaneous leishmaniasis.

Leishmania major infection in C57BL/6 mice is controlled by the activation of a Th1 response and nitric oxide (NO) production by macrophages. TNF-alpha is considered one of the most important cytokines involved in this response. In the present study, we investigated the expression of nitric oxide synthase (iNOS) in the inflammatory cells present in the lesion and draining lymph nodes, and the cytokine production by lymph node cells in animals treated with anti-TNF-alpha. Our results demonstrated that mice treated with anti-TNF-alpha presented an increase in the number of parasites and the size of lesion, but they were able to control the infection. The increase in the lesion size correlated to the reduction of iNOS activity in the draining lymph nodes. Furthermore, the anti-TNF-alpha treatment also reduced the expression of iNOS in the macrophages, but did not affect the iNOS expression in the neutrophils. The anti-TNF-alpha mAb did not reduce the iNOS expression in IFN-gamma-stimulated L. major infected neutrophils in vitro. Anti-TNF-alpha mAb treatment caused an increase in the production of IFN-gamma and IL-10 by the lymph node cells from infected mice. Consequently, these results suggest that neutrophils do not respond to anti-TNF-alpha treatment and might be a source of NO to control L. major infection under these experimental conditions.

Resolution of an infection with Leishmania braziliensis confers complete protection to a subsequent challenge with Leishmania Major in BALB/c mice

Both Leishmania major and L. braziliensis induce cutaneous leishmaniasis in BALB/c mice. Whereas BALB/c mice die of infection with L. major, they cure an infection with L. braziliensis. We report here that after curing an infection with L. braziliensis, BALB/c mice are resistant to challenge with L. major. When challenged with L. major, L. braziliensis pre-treated BALB/c mice mounted a delayed-type hypersensitivity response to L. major and produced high amounts of interferon-gamma (IFN-gamma) but low amounts of interleukin-4. The IFN-gamma produced by the L. braziliensis pre-infected mice was involved in the protection seen against L. major challenge since treating the mice with a neutralizing anti-IFN-gamma abrogated the protection. This suggests that cross-reactive antigen epitopes exist between L. braziliensis and L. major and that pre-infection with L. braziliensis primes BALB/c mice to epitopes on L. major that can elicit a protective Th1 response to the parasite.