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No description available.

Allergic asthma is an immunological disease, mediated by CD4+ Th2 cells, and its prevalence has increased over recent decades. Features of allergic asthma include airway hyperresponsiveness (AHR), airway eosinophilia, excessive airway mucus production, and increased IgE and Th2 cytokine levels. Airway remodeling with pulmonary fibrosis is noted in the progress of asthma. In this thesis, a murine model of allergic asthma was used to investigate the effect of cyclophosphamide (CY) on asthma and the involvement of regulatory T cells (Treg), and the role of Granulocyte-macrophage colony stimulating-factor (GM-CSF) in allergic asthma by using GM-CSF knockout mice. CY is a cytotoxic agent, which paradoxically augments several immune responses. The first part of this thesis was aimed to study the effects of CY in a murine model of allergic airway inflammation. BALB/c mice were immunized with ovalbumin (OVA) on days 0 and 14, and challenged with aerosolized OVA from days 21 to 27. Some mice additionally received CY on days -2 and 12. In the CY-treated animals, pronounced worsening of inflammatory features was noted, including increases in eosinophil infiltration, epithelial thickness, mucus occlusion and eosinophil numbers in bronchoalveolar lavage fluid (BALF). Increased total and OVA-specific serum IgE were also noted in the CY-treated animals. In cell cultures from peritracheal lymph nodes, the Th2 cytokines IL-4 and IL-5 were elevated in animals treated with CY. It was hypothesized that the effects of CY could be caused by reduced immunosuppression mediated by Treg. mRNA expression of the immunosuppressive cytokines IL-10 and TGF-beta was reduced in the lungs of CY-treated mice. The expression of FoxP3, a marker of naturally occurring Treg, was significantly reduced in spleens, thymuses and peritracheal lymph nodes after the second injection of CY, and in the lung tissue after allergen challenge in CY-treated mice. Furthermore, lung IL-10-producing CD4+ T cells and CTLA-4+-bearing CD4+ T cells were reduced after allergen aerosol challenge in CY-treated mice. Thus CY worsened the features of allergic pulmonary inflammation in this model, in association with increased production of IgE and Th2 cytokines. The reduction in expression of FoxP3 and immunosuppressive cytokines by CY suggests that toxicity to Treg may contribute to the increased inflammation. GM-CSF plays a role in the growth, development, and maturation of bone marrow hemopoietic cells into mature blood cells, and has been proposed to be involved in potentiating the function of inflammatory cells in allergic inflammation. In the second part of this thesis, GM-CSF knockout (KO) mice were used to investigate the role of GM-CSF. In allergic KO mice, airway eosinophils were only shown in the perivascular, but not peribronchial areas in the lung, compared to the allergic wild-type (WT) mice in which eosinophil infiltration appeared in both areas. Eosinophil numbers were drastically reduced in the bronchoalveolar lavage fluid (BALF) of KO mice. IL-5 production in the lung tissue and BALF in allergic KO mice was reduced; similar results were also found in peritracheal draining lymph nodes after in vitro stimulation assays. However, IL-4 and IL-13 production, airway hyperresponsiveness (AHR), and serum IgE production were not affected in allergic KO mice. Surprisingly, lung IFN-gamma mRNA and BALF levels were increased in allergic KO mice. Lung mRNA levels of CCR3, a key chemokine receptor on eosinophils, were significantly reduced in allergic KO mice, whereas expression of the chemokines eotaxin and RANTES were at similar levels in allergic KO and WT mice. Lung mRNA levels of the IFN-gamma-inducible chemokines Mig (CXCL9) and IP-10 (CXCL10), which are antagonists of CCR3, and their receptor CXCR3 were increased in allergic KO mice, compared with allergic WT mice. Data obtained from flow cytometry showed more eosinophils survived in the lung of WT mice than KO mice. Another allergy model, a peritoneal allergy model was performed to investigate inflammation in a different model. Leukocyte subpopulations such as neutrophils, eosinophils, macrophages, and lymphocytes were reduced in the peritoneal lavage fluid of allergic KO mice. The findings revealed that GM-CSF is essential for IL-5 production, pulmonary airway eosinophilia and eosinophil survival. In the absence of GM-CSF, over-production of IFN-???? may induce chemokines, including Mig and IP-10, which are antagonists for CCR3 and may reduce airway eosinophil infiltration. In this thesis, a murine model of allergic asthma has been used to obtain novel findings on the regulation of allergic inflammation. The results with CY are relevant to the treatment of asthma patients with CY and other cytotoxic agents. The findings in the GM-CSF KO mice suggest that GM-CSF is a potential therapeutic target in asthma, and that in assessment of new therapeutic agents for asthma, effects on GM-CSF should be considered.

<p>This study shows that herbs can be effectively screened for potiential bio-activity using in vitro methods. Further studies will be needed to better explore Artemisia afra&rsquo / s effect on immunoregulation, particularly long term effects of the herb on the immune system and its effect on other disease states.</p>

Bei IL-10 handelt es sich um ein antiinflammatorisches Zytokin, dessen immunmodulatorische Effekte bereits in zahlreichen Studien aufgezeigt werden konnten. Ziel dieser Studie war, die Unterschiede in der systemischen Inflammation und Organdysfunktion an Mäusen zu untersuchen, die nach Induktion eines hämorrhagischen Schocks, entweder inhalativ oder systemisch, mit IL-10 behandelt wurden. Männliche C57/BL6 Mäuse (6 Tiere pro Gruppe) wurden für 1.5 Stunden blutdruckkontrolliert in einen hämorrhagischen Schock versetzt. Nach anschließender Volumensubstitution wurde ihnen inhalativ oder intraarteriell rekombiniertes Maus - IL-10 verabreicht. Nach einer Gesamtversuchsdauer von 6 - bzw. 24 Stunden erfolgte die Tötung der Tiere. Die Ergebnisse der Studie zeigen, dass die lokale und systemische Verabreichung von IL-10 das Zytokinprofil der systemischen Inflammationsantwort unterschiedlich beeinflusst. Die Lunge kann durch inhalative Gabe von IL-10 geschützt werden, ohne die systemische Inflammationsantwort zu beeinflussen.

<p>This study shows that herbs can be effectively screened for potiential bio-activity using in vitro methods. Further studies will be needed to better explore Artemisia afra&rsquo / s effect on immunoregulation, particularly long term effects of the herb on the immune system and its effect on other disease states.</p>

Allergic asthma is an immunological disease, mediated by CD4+ Th2 cells, and its prevalence has increased over recent decades. Features of allergic asthma include airway hyperresponsiveness (AHR), airway eosinophilia, excessive airway mucus production, and increased IgE and Th2 cytokine levels. Airway remodeling with pulmonary fibrosis is noted in the progress of asthma. In this thesis, a murine model of allergic asthma was used to investigate the effect of cyclophosphamide (CY) on asthma and the involvement of regulatory T cells (Treg), and the role of Granulocyte-macrophage colony stimulating-factor (GM-CSF) in allergic asthma by using GM-CSF knockout mice. CY is a cytotoxic agent, which paradoxically augments several immune responses. The first part of this thesis was aimed to study the effects of CY in a murine model of allergic airway inflammation. BALB/c mice were immunized with ovalbumin (OVA) on days 0 and 14, and challenged with aerosolized OVA from days 21 to 27. Some mice additionally received CY on days -2 and 12. In the CY-treated animals, pronounced worsening of inflammatory features was noted, including increases in eosinophil infiltration, epithelial thickness, mucus occlusion and eosinophil numbers in bronchoalveolar lavage fluid (BALF). Increased total and OVA-specific serum IgE were also noted in the CY-treated animals. In cell cultures from peritracheal lymph nodes, the Th2 cytokines IL-4 and IL-5 were elevated in animals treated with CY. It was hypothesized that the effects of CY could be caused by reduced immunosuppression mediated by Treg. mRNA expression of the immunosuppressive cytokines IL-10 and TGF-beta was reduced in the lungs of CY-treated mice. The expression of FoxP3, a marker of naturally occurring Treg, was significantly reduced in spleens, thymuses and peritracheal lymph nodes after the second injection of CY, and in the lung tissue after allergen challenge in CY-treated mice. Furthermore, lung IL-10-producing CD4+ T cells and CTLA-4+-bearing CD4+ T cells were reduced after allergen aerosol challenge in CY-treated mice. Thus CY worsened the features of allergic pulmonary inflammation in this model, in association with increased production of IgE and Th2 cytokines. The reduction in expression of FoxP3 and immunosuppressive cytokines by CY suggests that toxicity to Treg may contribute to the increased inflammation. GM-CSF plays a role in the growth, development, and maturation of bone marrow hemopoietic cells into mature blood cells, and has been proposed to be involved in potentiating the function of inflammatory cells in allergic inflammation. In the second part of this thesis, GM-CSF knockout (KO) mice were used to investigate the role of GM-CSF. In allergic KO mice, airway eosinophils were only shown in the perivascular, but not peribronchial areas in the lung, compared to the allergic wild-type (WT) mice in which eosinophil infiltration appeared in both areas. Eosinophil numbers were drastically reduced in the bronchoalveolar lavage fluid (BALF) of KO mice. IL-5 production in the lung tissue and BALF in allergic KO mice was reduced; similar results were also found in peritracheal draining lymph nodes after in vitro stimulation assays. However, IL-4 and IL-13 production, airway hyperresponsiveness (AHR), and serum IgE production were not affected in allergic KO mice. Surprisingly, lung IFN-gamma mRNA and BALF levels were increased in allergic KO mice. Lung mRNA levels of CCR3, a key chemokine receptor on eosinophils, were significantly reduced in allergic KO mice, whereas expression of the chemokines eotaxin and RANTES were at similar levels in allergic KO and WT mice. Lung mRNA levels of the IFN-gamma-inducible chemokines Mig (CXCL9) and IP-10 (CXCL10), which are antagonists of CCR3, and their receptor CXCR3 were increased in allergic KO mice, compared with allergic WT mice. Data obtained from flow cytometry showed more eosinophils survived in the lung of WT mice than KO mice. Another allergy model, a peritoneal allergy model was performed to investigate inflammation in a different model. Leukocyte subpopulations such as neutrophils, eosinophils, macrophages, and lymphocytes were reduced in the peritoneal lavage fluid of allergic KO mice. The findings revealed that GM-CSF is essential for IL-5 production, pulmonary airway eosinophilia and eosinophil survival. In the absence of GM-CSF, over-production of IFN-???? may induce chemokines, including Mig and IP-10, which are antagonists for CCR3 and may reduce airway eosinophil infiltration. In this thesis, a murine model of allergic asthma has been used to obtain novel findings on the regulation of allergic inflammation. The results with CY are relevant to the treatment of asthma patients with CY and other cytotoxic agents. The findings in the GM-CSF KO mice suggest that GM-CSF is a potential therapeutic target in asthma, and that in assessment of new therapeutic agents for asthma, effects on GM-CSF should be considered.

Estudos epidemiológicos e moleculares têm sugerido que o HPV é o principal fator de risco para o desenvolvimento de lesões malignas na cérvice uterina. E, sendo o número de infecções extremamente maior do que o número de casos de câncer cervical, este fato nos leva à investigação de outros fatores associados, como por exemplo, a predisposição imunológica do hospedeiro. Este estudo tem como objetivo avaliar a associação dos polimorfismos (-1082A/G) e (-308 A/G), localizados nos genes da IL-10 e TNF-α, respectivamente, com a infecção genital pelo Papilomavírus Humano (HPV), incluindo os tipos oncogênicos HPV-16, 18 e 31, visto que, estas citocinas são moléculas importantes na resposta imune contra infecções virais. Trata-se de um estudo de casos e controles. O grupo controle foi composto por 211 mulheres, que apresentavam resultado negativo para infecção genital por HPV, identificada através da técnica de Reação em Cadeia da Polimerase (PCR) e exame citopatológico sem alterações. Já os casos, corresponderam a 84 mulheres com infecção genital por HPV e resultado anatomopatológico alterado. A técnica de amplificação refratária de mutações (ARMS-PCR) foi utilizada para a identificação dos polimorfismos. Regressão logística múltipla foi utilizada para verificar a associação das variáveis estudadas com o desfecho (infecção genital pelo HPV).O cálculo de Equilíbrio de Hardy-Weinberg foi utilizado para verificar se as freqüências alélicas e gentotípicas observadas estão de acordo com as esperadas na população em estudo. Para os resultados de IL-10, a freqüência genotípica observada nos casos foi de 11,9% (AA), 28,6% (AG) e 59,5% (GG); a freqüência alélica foi de 26,0% para A e 74,0% para G. No grupo controle, a freqüência genotípica encontrada foi 22,8% (AA), 48,8% (AG) e 28,4% (GG); a freqüência alélica foi de 47,0% para A e 53,0% para G. Houve diferença significativa entre os grupos estudados, tanto para a freqüência alélica quanto para a genotípica (p<0,0001). Entre as mulheres com infecção, encontramos associação das lesões intraepiteliais escamosas de baixo grau (LGSIL) com o genótipo GG (p=0,02). As variáveis idade (RC=4,70; IC95%: 2,61-8,40), co-infecção por HIV (RC=11,21; IC95%:1,002-125,33) e o genótipo GG (RC=4,22; IC95%: 1,84-9,61) permaneceram independentemente associados ao desfecho (infecção genital pelo HPV). Para TNF-α, a homozigosidade do alelo G (genótipo GG) foi encontrada em maior freqüência nos casos (36,9%), seguido por 35,7% do genótipo AA e 27,4% do genótipo AG. Houve diferença significativa entre os grupos estudados, tanto para a freqüência alélica (p<0,0002) quanto para a genotípica: AA (p=0,03), AG e GG (p<0,0001). Analisando a associação com lesões cervicais e tipos oncogênicos, encontramos associação entre o genótipo GG e LGSIL (p<0,01). O genótipo GG está associado ao tipo oncogênico HPV-16 (p<0,05), e à co-infecção pelo vírus HIV (p<0,001). As variáveis idade (RC=3,46; IC95%: 1,89-6,33), os genótipos AG (RC=9,21; IC95%: 4,29-19,75) e AA (RC=2,73; IC95%: 1,25-6,00) permaneceram independentemente associados ao desfecho (infecção genital pelo HPV). Com estes resultados, é possível sugerir que a predisposição determinada geneticamente para a produção de altos níveis de IL-10 e TNF-α parece estar associada à infecção genital pelo HPV, mostrando a importância da resposta imunológica do hospedeiro no processo de infecção e na progressão das lesões cervicais geradas pelo Papilomavírus Humano. / Molecular and epidemiological studies have suggested that HPV is the most important risk factor for the development of malignant lesions in the uterine cervix. The fact that the number of HPV infections is extremely greater than the number of cervical cancer cases leads us to the investigation of other risk factors, such as the predisposition of the host immune. The present study aimed to evaluate the influence of genetic polymorphisms (-1082A/G) and (-308A/G), located in the genes of IL-10 and TNF-α, respectively, with the genital HPV infection, including oncogenic HPV-16, 18 and 31, since these cytokines are important molecules in the immune response against viral infections. This is a case-control study. The control group was composed by 211 women, who have tested negative for HPV genital infection by the Polymerase Chain Reaction (PCR) technique, and who had normal cytologic results. Cases were 84 women with HPV genital infection and abnormal anatomopathological results. The technique of amplification refractory mutation system (ARMS-PCR) was used to identify the polymorphisms. Multiple logistic regression was used to verify the association between the study factors and the outcome (genital infection by HPV). The Hardy-Weinberg equilibrium was used to verify whether the observed allelic and genotypic frequencies were according with the expected in the studied population. For the results of IL-10, the genotypic frequencies observed in the group of women with infection was 11.9% (AA), 28,6% (AG) and 59.5% (GG), the allelic frequency was 26.0% for 74.0% for A and G. In the control group, the frequency was found genotypical 22.8% (AA), 48.8% (AG) and 28.4% (GG), the allelic frequency was 47.0% to 53.0% for A and G. There were significant differences between groups, both for the allelic frequency as for the genotypic (p<0.0001). Among women with infection, we found association of injuries LGSIL with the GG genotype (p=0021). The variables age (OR=4.70; 95%IC: 2.61-8.40), HIV co-infection (OR=11.21; 95%IC: 1.002-125,33), and genotype GG (OR=4.22; 95%IC: 1.84-9.61) remained independently associated to the outcome (genital HPV infection). For TNF-α analysis, the genotypic frequencies observed in the group of patients was 22.0% (AA), 69.0% (AG) and 8.0% (GG), the allelic frequency was 57.0% and 43.0% for A to G. In the control group, the frequency genotype was found 35.0% (AA), 27.0% (AG) and 36.0% (GG), the allelic frequency was 49.0% for A and 51.0% for G. There were significant differences between groups, both for the allelic frequency (p<0.0002) and to the genotypic: AA (p=0.03), AG e GG (p<0.0001). Analysing the association with cervical lesions and with high-risk type, there was found a significant association, between the genotype GG and LGSIL (p<0.01). The genotype GG is associated with the HPV-16 infection (p<0.05) and with the HIV virus co-infection (p<0001). The variables age (OR=3.46; 95%IC: 1.89-6.33), genotypes AG (OR=9.21; 95%IC: 4.29-19.75) and AA (OR=2.73; 95%IC: 1.25- 6.00) remained independently associated to the outcome (genital HPV infection). The results suggest that the genetically determined predisposition to produce high levels of IL- 10 and TNF-α may be related to the genital HPV infection showing the importance of the host immune response in the progression of cervical lesions caused by the Human Papillomavirus.

A dor neuropática (DN) é causada por uma lesão primária ou por uma disfunção no sistema nervoso periférico (SNP) ou central (SNC), sendo que os principais sintomas são a alodinia mecânica e a hiperalgesia a estímulos térmicos e mecânicos. A DN apresenta resposta analgésica insuficiente com terapeuticas farmacológicas clássicas, sendo um desafio para o tratamento clínico. Técnicas de neuromodulação central, como a estimulação transcraniana por corrente contínua (ETCC), representam um recurso promissor no manejo da dor, uma vez que promovem neuroplasticidade em vias envolvidas com o processo doloroso, sendo um método não-invasivo que pode ser combinado com outras terapias. Sendo assim, o objetivo deste estudo foi investigar os efeitos do tratamento repetido com ETCC na resposta hiperalgésica térmica e mecânica em modelo experimental de DN. Adicionalmente, foram avaliados os níveis de IL-1β, IL-10, TNF-α e NGF em estruturas do SNC destes animais. Todos os procedimentos foram aprovado pela Comissão de Ética no Uso de Animais (CEUA/HCPA:120512). Oitenta e quatro ratos machos Wistar foram divididos em 7 grupos: controle, dor neuropática, dor neuropática+ETCC, dor neuropática+sham ETCC, sham dor neuropática, sham dor neuropática+ETCC e sham dor neuropática+sham ETCC. O modelo de DN foi induzido por meio de ligura parcial do nervo isquiático na pata esquerda. O sham do modelo de DN seguiu o mesmo protocolo, com simulação da ligadura parcial do nervo isquiático e o grupo controle não sofreu nenhuma manipulação. O tratamento com ETCC consistiu em 20minutos/dia/8 dias, com intensidade de 0,5mA. Para o sham do tratamento, os eletrodos foram apenas fixados à cabeça do animal durante 20 minutos/dia/8 dias, sem nenhuma estimulação. A hiperalgesia térmica e mecânica foi avaliada por meio dos testes da Placa Quente e de Von Frey, respectivamente, no tempo basal, 7 e 14 dias após a cirurgia e imediatamente, 24 horas e 7 dias após o final do tratamento. Os níveis de IL-1β, IL-10, TNF-α e NGF no cortex cerebral, medula espinhal e tronco cerebral foram determinados por ELISA 48 horas e 7 dias após o final do tratamento. A análise estatística para os testes nociceptivos foi realizada através da Generalized Estimation Equation (GEE)/Bonferroni e para as análises bioquímicas por ANOVA de uma via (IL-1β, IL-10, TNF-α ) e ANOVA de três vias (NGF). Os dados estão expressos como media+erro padrão da média, sendo considerado significativo p<0.05. Nossos resultados demonstraram que a DN altera os níveis de IL-1β, IL-10, TNF-α e NGF no SNC em curto e longo prazo. Além disso, a ETCC reduz a resposta nociceptiva a curto e longo prazo e na modulação dos níveis de citocinas no sistema nervoso central neste modelo. Evidencia-se a importância do papel do sistema imune central nos processos de continuidade da dor neuropática, que pode estar envolvido com as alterações neuroplásticas maladaptativas características dessa patologia. / Neuropathic pain (NP) is caused by a primary insult or dysfunction in the central or peripheral nervous system and its prevalence depends on the type of trauma and related dysfunction. The main symptoms are mechanical allodynia and hyperalgesia to both mechanical and thermal stimuli. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment and scientific research; and the search for new therapies for this pathology is of fundamental important. Central neuromodulation techniques, such as transcranial direct current stimulation (tDCS), represent a promising resource to pain management since they promote neuroplasticity in the central system of pain. Moreover, tDCS has the advantages of being a noninvasive technique and can be combined with other interventions. The aim of this study was investigated the effects of tDCS in the thermal and mechanical hyperalgesia induced by chronic constriction injury (CCI) of sciatic nerve and measured its effect on the neurochemical markers (IL-1β, IL-10, TNF-α, and NGF levels) on central nervous system structures. All experiments and procedures were approved by the Institutional Animal Care and Use Committee (GPPG-HCPA No.120512) and performed in accordance with the Guide for the Care and Use of Laboratory Animals 8th ed. The CCI of sciatic nerve was used for the induction of NP. For sham surgery, the sciatic nerve was exposed similarly, but it was not ligated. The control group did not undergo surgical procedure. After the establishment of NP, the rats of treated groups were subjected to a 20 minutes session of anodal tDCS, every afternoon for eight days, under a direct constant current of 0.5 mA intensity. The thermal and mechanical hyperalgesia was assessed by Hot plate and Von Frey test, respectively, and evaluated on baseline, 7 and 14 days after surgery; immediately, 24 hours and 7 days after treatment. The IL-1β, IL-10, TNF-α and NGF levels on cortex, spinal cord and brainstem were determined by sandwich-ELISA at 48 hours and 7 days after the end of treatment. Data were expressed as the mean±standard error of the mean (S.E.M). Generalized Estimating Equation (GEE) followed by Bonferroni was performed to compare all groups in different times of nociceptive tests and to biochemical data the one-way ANOVA was used to compare the IL-1β, IL-10, TNF-α and three-way ANOVA was used to compare the NGF levels. P-values less than 0.05 were considered significant. SPSS 19.0 for Windows was used for statistical analysis. In summary, we showed that anodal tDCS is effective to relieve NP and modulate cytokine in CCI rat model, and its effect is observed at long-term. In addition, the CCI model induced increased NGF levels in cerebral cortex and spinal cord at long-lasting time, evidencing the important feature of this neurotrophin in neuropathic pain condition. Additionally, we observed an important role of the central immune system in the neuropathic process, which can be involved with the maladaptative neuroplastic changes.

Estudos epidemiológicos e moleculares têm sugerido que o HPV é o principal fator de risco para o desenvolvimento de lesões malignas na cérvice uterina. E, sendo o número de infecções extremamente maior do que o número de casos de câncer cervical, este fato nos leva à investigação de outros fatores associados, como por exemplo, a predisposição imunológica do hospedeiro. Este estudo tem como objetivo avaliar a associação dos polimorfismos (-1082A/G) e (-308 A/G), localizados nos genes da IL-10 e TNF-α, respectivamente, com a infecção genital pelo Papilomavírus Humano (HPV), incluindo os tipos oncogênicos HPV-16, 18 e 31, visto que, estas citocinas são moléculas importantes na resposta imune contra infecções virais. Trata-se de um estudo de casos e controles. O grupo controle foi composto por 211 mulheres, que apresentavam resultado negativo para infecção genital por HPV, identificada através da técnica de Reação em Cadeia da Polimerase (PCR) e exame citopatológico sem alterações. Já os casos, corresponderam a 84 mulheres com infecção genital por HPV e resultado anatomopatológico alterado. A técnica de amplificação refratária de mutações (ARMS-PCR) foi utilizada para a identificação dos polimorfismos. Regressão logística múltipla foi utilizada para verificar a associação das variáveis estudadas com o desfecho (infecção genital pelo HPV).O cálculo de Equilíbrio de Hardy-Weinberg foi utilizado para verificar se as freqüências alélicas e gentotípicas observadas estão de acordo com as esperadas na população em estudo. Para os resultados de IL-10, a freqüência genotípica observada nos casos foi de 11,9% (AA), 28,6% (AG) e 59,5% (GG); a freqüência alélica foi de 26,0% para A e 74,0% para G. No grupo controle, a freqüência genotípica encontrada foi 22,8% (AA), 48,8% (AG) e 28,4% (GG); a freqüência alélica foi de 47,0% para A e 53,0% para G. Houve diferença significativa entre os grupos estudados, tanto para a freqüência alélica quanto para a genotípica (p<0,0001). Entre as mulheres com infecção, encontramos associação das lesões intraepiteliais escamosas de baixo grau (LGSIL) com o genótipo GG (p=0,02). As variáveis idade (RC=4,70; IC95%: 2,61-8,40), co-infecção por HIV (RC=11,21; IC95%:1,002-125,33) e o genótipo GG (RC=4,22; IC95%: 1,84-9,61) permaneceram independentemente associados ao desfecho (infecção genital pelo HPV). Para TNF-α, a homozigosidade do alelo G (genótipo GG) foi encontrada em maior freqüência nos casos (36,9%), seguido por 35,7% do genótipo AA e 27,4% do genótipo AG. Houve diferença significativa entre os grupos estudados, tanto para a freqüência alélica (p<0,0002) quanto para a genotípica: AA (p=0,03), AG e GG (p<0,0001). Analisando a associação com lesões cervicais e tipos oncogênicos, encontramos associação entre o genótipo GG e LGSIL (p<0,01). O genótipo GG está associado ao tipo oncogênico HPV-16 (p<0,05), e à co-infecção pelo vírus HIV (p<0,001). As variáveis idade (RC=3,46; IC95%: 1,89-6,33), os genótipos AG (RC=9,21; IC95%: 4,29-19,75) e AA (RC=2,73; IC95%: 1,25-6,00) permaneceram independentemente associados ao desfecho (infecção genital pelo HPV). Com estes resultados, é possível sugerir que a predisposição determinada geneticamente para a produção de altos níveis de IL-10 e TNF-α parece estar associada à infecção genital pelo HPV, mostrando a importância da resposta imunológica do hospedeiro no processo de infecção e na progressão das lesões cervicais geradas pelo Papilomavírus Humano. / Molecular and epidemiological studies have suggested that HPV is the most important risk factor for the development of malignant lesions in the uterine cervix. The fact that the number of HPV infections is extremely greater than the number of cervical cancer cases leads us to the investigation of other risk factors, such as the predisposition of the host immune. The present study aimed to evaluate the influence of genetic polymorphisms (-1082A/G) and (-308A/G), located in the genes of IL-10 and TNF-α, respectively, with the genital HPV infection, including oncogenic HPV-16, 18 and 31, since these cytokines are important molecules in the immune response against viral infections. This is a case-control study. The control group was composed by 211 women, who have tested negative for HPV genital infection by the Polymerase Chain Reaction (PCR) technique, and who had normal cytologic results. Cases were 84 women with HPV genital infection and abnormal anatomopathological results. The technique of amplification refractory mutation system (ARMS-PCR) was used to identify the polymorphisms. Multiple logistic regression was used to verify the association between the study factors and the outcome (genital infection by HPV). The Hardy-Weinberg equilibrium was used to verify whether the observed allelic and genotypic frequencies were according with the expected in the studied population. For the results of IL-10, the genotypic frequencies observed in the group of women with infection was 11.9% (AA), 28,6% (AG) and 59.5% (GG), the allelic frequency was 26.0% for 74.0% for A and G. In the control group, the frequency was found genotypical 22.8% (AA), 48.8% (AG) and 28.4% (GG), the allelic frequency was 47.0% to 53.0% for A and G. There were significant differences between groups, both for the allelic frequency as for the genotypic (p<0.0001). Among women with infection, we found association of injuries LGSIL with the GG genotype (p=0021). The variables age (OR=4.70; 95%IC: 2.61-8.40), HIV co-infection (OR=11.21; 95%IC: 1.002-125,33), and genotype GG (OR=4.22; 95%IC: 1.84-9.61) remained independently associated to the outcome (genital HPV infection). For TNF-α analysis, the genotypic frequencies observed in the group of patients was 22.0% (AA), 69.0% (AG) and 8.0% (GG), the allelic frequency was 57.0% and 43.0% for A to G. In the control group, the frequency genotype was found 35.0% (AA), 27.0% (AG) and 36.0% (GG), the allelic frequency was 49.0% for A and 51.0% for G. There were significant differences between groups, both for the allelic frequency (p<0.0002) and to the genotypic: AA (p=0.03), AG e GG (p<0.0001). Analysing the association with cervical lesions and with high-risk type, there was found a significant association, between the genotype GG and LGSIL (p<0.01). The genotype GG is associated with the HPV-16 infection (p<0.05) and with the HIV virus co-infection (p<0001). The variables age (OR=3.46; 95%IC: 1.89-6.33), genotypes AG (OR=9.21; 95%IC: 4.29-19.75) and AA (OR=2.73; 95%IC: 1.25- 6.00) remained independently associated to the outcome (genital HPV infection). The results suggest that the genetically determined predisposition to produce high levels of IL- 10 and TNF-α may be related to the genital HPV infection showing the importance of the host immune response in the progression of cervical lesions caused by the Human Papillomavirus.