Background: Obesity-associated metabolic complications display sexual dimorphism and can be impacted by cytokines. We previously showed that interleukin-10 (IL-10) was upregulated in white adipose tissue (WAT) of obese women with type 2 diabetes (T2D). Whether this pertains to men is unknown. The aim of this study was to compare the impact of obesity and T2D on WAT IL- 10 levels in men versus women. Methods: Plasma and subcutaneous WAT biopsies were obtained from 108 metabolically well-characterized individuals. WAT IL10 expression/secretion and WAT-resident IL-10-secreting macrophage number were measured. Circulating sex hormone levels were correlated toWAT IL10 expression in 22 individuals and sex hormone effects on macrophage IL10 expression were investigated in vitro. Results: Obese women with T2D showed increased IL10 expression/secretion and IL-10-secreting WAT macrophage number compared to other female groups. This difference was absent in men. Non-obese women and men with T2D showed similar IL-10 levels compared to healthy controls, indicating that T2D alone does not regulate IL-10. Although WAT IL10 expression correlated with serum estrone (E1) concentrations, recombinant E1 did not affect macrophage IL10 expression in vitro. Conclusion: WAT IL-10 levels are higher in women with obesity and T2D, but not in men and this effect is primarily attributed to obesity per se. This is less likely to be driven by circulating sex hormones. We propose that the WAT IL-10 might exert protective effects in obesity-associated chronic inflammation in women which could be one of the contributing factors for the decreased morbidity observed in women during obesity than men.

No description available.

No description available.

No description available.

Metal-induced autoimmunity is an experimental model of environmentally induced autoimmune syndrome. Subtoxic doses of heavy metals administered to genetically susceptible mice resulted in the production of highly specific IgG antinucleolar antibodies (ANoA) accompanied by lymphoproliferation and serum increases in IgG1 and IgE. In this study, the induction of tolerance to mercuric chloride (HgCl2)-induced autoimmunity by pre-exposure to the low-dose mercury was reported. The ultimate mechanisms through which the immune system obtains the tolerance to a low dose of heavy metals remain unknown. The previous experiment showed that CD4+CD25+ regulatory T cells (Tregs) contributed to the maintenance of immunological self-tolerance and to the prevention of autoimmune diseases. The tolerized mice had a higher percentage of Tregs and ICOS+ regulatory T cells than the nontolerized mice. ICOS (Inducible T-cell COStimulator) is a costimulatory receptor homologous to CD28 and CTLA-4. The expression of ICOS occurs on activated T cells and is dependent upon TCR and CD28 signals. The anti-ICOS blockade restored the ability of tolerized mice to produce elevated amounts of IgG1, IgE and anti-nucleolar antibodies. The ICOS expression on Tregs and Teff cells increased after the mercury challenge. Mice that received anti-ICOS had a low percentage of Tregs and showed an increased production of several cytokines. Taken together, these results suggested that Tregs maintained the immune tolerance in response to chemical challenges. The ICOS pathway is important for the differentiation of Tregs and blocking this pathway could prevent peripheral tolerance to the low dose mercury. The results also showed the splenocytes from the tolerized group produced a higher amount of IL-10 than the nontolerized group. This promoted us to study the role of IL-10 in tolerance induction. To validate the role of Interleukin-10 in tolerance maintenance, the tolerized mice were treated with blocking anti-IL-10 and anti-IL-10 receptor mAb. Those tolerized mice treated with IL-10 blocking antibodies produced a higher amount of serum IgG1, IgE and anti-nucleolar antibodies compared with the group treated with control antibodies. This suggested IL-10 is critical in maintaining the peripheral tolerance in a mercury treated mouse model. All Trans retinoic acid (ATRA) is the metabolically active derivative of vitamin A and functions as potent regulator of gene expression. Vitamin A and retinoic acid play vital roles in the homeostatic control of the immune system because vitamin A-deficient individuals are incapable of controlling bacterial, viral, and protozoan diseases. In this study, the role of ATRA was reported in the first time in mercuric chloride (HgCl2)-induced autoimmunity by feeding the ASW mice ATRA. The results showed that retinoid acid exacerbated the mercury-induced autoimmunity. To study whether retinoic acid plays a role in low dose mercury induced tolerance, three groups of tolerized ASW mice were treated with either ATRA, mercury or both. The results showed retinoic acid could break the low-dose mercury-induced tolerance. The splenocytes from the group that received both mercury and ATRA treatment produced much more IL-2 and IFN-γ. This group had the lowest percentage of IL-10+ cells. The group that received ATRA had a lower percentage of early apoptosis cells. To further study the mechanism, a PCR array that included 84 genes, involved in T cell and B cell activation, was used to study four groups of mice treated with mercury, ATRA, both or neither. 10 candidate genes were selected and analyzed by Real-Time PCR to validate the PCR array results. Further study is needed to characterize the expression and the role of molecules that are upregulated by mercury and ATRA. / Microbiology and Immunology

M.tb, the causative agent of pulmonary tuberculosis (TB) remains one of the leading causes of infectious disease-based death worldwide. BCG, the only clinically approved TB vaccine, has been in use for almost a century to vaccinate against TB. Despite its success in protecting against disseminated forms of TB, it is unable to provide protection against pulmonary M.tb infection. Although there have been many recent efforts to enhance or replace BCG, our lack of understanding towards host immunity against M.tb has substantially hindered this goal. One aspect of pulmonary M.tb infection that remains poorly understood is the induction of Th1 immunity, which is substantially delayed in comparison to other pulmonary infections. This allows the bacteria to establish an infectious foothold within the host and impairs the ability of the host to clear the infection. Given the importance of the innate immune response in the induction of adaptive immunity, this delay in the establishment of Th1 immunity following pulmonary M.tb infection is likely due to a defect in the early innate immune response. However, the specific roles of this immune compartment in regards to T cell activation following pulmonary M.tb infection is still not well understood. As such, the scope of this thesis is to gain an increased understanding towards the role of the innate immune compartment in the generation of Th1 responses. Such insights will allow us to develop new strategies to improve upon future and existing TB vaccine design. / Thesis / Doctor of Philosophy (PhD)

Filarien persistieren bis zu 15 Jahren in ihren Wirten. Als eine Ursache dieser Persistenz diskutiert man die Fähigkeit der Filarien, die Immunantwort des Wirtes gezielt zu modulieren und eine zelluläre Hyporeaktivität zu induzieren. In der vorliegenden Arbeit wurde untersucht, ob ein sezernierter Cysteinproteasen-Inhibitor (Onchocystatin) der humanpathogenen Filarie Onchocerca volvulus immunmodulierende Eigenschaften besitzt und an der Herausbildung eines hyporeaktiven Immunstatus des Wirtes beteiligt ist. Für die Untersuchungen wurde Onchocystatin als full length Molekül (rOv17) und als verkürztes Molekül (trOv17) rekombinant hergestellt. Das verkürzte trOv17 besitzt aufgrund des Fehlens des N-terminalen Bereiches eine verminderte proteaseinhibitorische Aktivität. Die in vitro Studien mit den rekombinant hergestellten O. volvulus Cystatinen verdeutlichen, daß rOv17 und auch trOv17 potente Immunmodulatoren sind, die sowohl die antigenspezifische als auch die polyklonal-stimulierte Proliferation von humanen PBMC inhibieren. Die zelluläre Hyporeaktivität ist dabei auf die Modulation von Monozytenfunktionen zurückzuführen. rOv17 und trOv17 modulieren die Antigenpräsentation, die Zytokinproduktion und die Expression kostimulatorischer Signale von humanen Monozyten. So konnte gezeigt werden, daß rOv17 und trOv17 die Aktivität von humanem Cathepsin L und S inhibieren und die Expression von HLA-DR, CD40 und CD86 vermindern. Die Modulation der Zytokinproduktion durch rOv17 und trOv17 ist durch eine verstärkte TNF-alpha und IL-10 Produktion und durch eine verminderte IL-12 Produktion charakterisiert. Desweiteren konnte in Neutralisationsstudien mit anti-IL-10 Ak gezeigt werden, daß die verminderte Expression von HLA-DR, CD40 und CD86 Folge der durch rOv17 und trOv17 induzierten verstärkten IL-10 Produktion ist. Im Gegensatz dazu bleibt die verminderte IL-12 Produktion und die verminderte polyklonal-stimulierte Proliferation humaner PBMC auch nach der Neutralisation von IL-10 bestehen. Die Studien mit den rekombinant hergestellten O. volvulus Cystatinen zeigen, daß rOv17 und trOv17 ihr immunologisches Umfeld auf vielfältige Art und Weise modulieren. Dabei spielt vermutlich die Inhibition der Aktivität einer Wirtscysteinprotease, aber auch ein von der Funktion als Cysteinproteasen-Inhibitor unabhängiger Mechanismus eine Rolle. Der Cysteinproteasen-Inhibitor der Filarie O. volvulus besitzt somit die Eigenschaft, die Immunantwort des Wirtes zu modifizieren, und ist vermutlich eine wesentliche Komponente, die dem Parasiten eine lange Persistenz im Wirt ermöglicht. / Immune responses of individuals infected with filarial nematodes are characterized by a marked cellular hyporesponsiveness. The establishment of this hyporesponsiveness is considered as an important mechanism to avoid host immune responses which could eliminate the parasites. The present study is investigating the immunomodulatory potential of a 17 kD secreted cysteine protease inhibitor (onchocystatin) of the human pathogenic filaria Onchocerca volvulus. In vitro studies using recombinant onchocystatin (rOv17) identified this inhibitor as a potent immunomodulator. rOv17 suppresses the antigen-driven and the polyclonally-stimulated proliferation of human PBMC. This cellular hyporeactivity is due to the modulation of monocytic function by rOv17, comprising the modulation of antigenpresentation, the expression of costimulatory molecules and the production of cytokines. Thus rOv17 strongly inhibits the activity of human cathepsin L and S and reduces the expression of MHC class II molecules as well as the expression of CD40 and CD86 on human monocytes. The modulation of cytokine production by rOv17 is characterized by an initial increase of TNF-alpha which is followed by an increase of IL-10 and a decrease of IL-12. By neutralization studies it was shown that the suppression of MHC class II molecules and of CD86 and CD40 is mediated by the rOv17 induced increase of IL-10. In contrast cellular hyporeactivity and the reduced IL-12 production remain unaffected by neutralization of IL-10. In comparison to rOv17 a truncated onchocystatin (trOv17) with lowered protease inhibitory activity was investigated. Surprisingly even trOv17 is immunomodulatory active suggesting that immunomodulation by onchocystatin is mediated by both an inhibitor-dependent and an inhibitor-independent mechanism. These data demonstrate that onchocystatin is a potent immunomodulator of host immune responses and in consequence is an essential component that enables the parasites a long persistence within their hosts.

O glioblastoma (GBM) é o tumor cerebral primário mais comum e o mais grave tumor de células da glia. O GBM é um tumor astrocítico de grau IV caracterizado pela proliferação descontrolada, infiltrado difuso, tendência à necrose, angiogênese, resistência a apoptose e grande heterogeneidade genética. Apesar da terapia abranger a remoção cirúrgica máxima, a radioterapia e a quimioterapia, o tumor torna-se resistente à drogas utilizadas no tratamento levando o paciente a recorrência e morte em menos de 15 meses após o diagnóstico. Uma alternativa para o tratamento do GBM é a imunoterapia, a qual é capaz de estimular o sistema imunológico do próprio paciente a gerar uma resposta específica e duradoura que pode proteger contra a recorrência da doença. Uma dessas alternativas envolve o uso de vacinas de DNA codificando antígenos tumorais e proteínas imunomoduladoras capazes de ativar eficientemente linfócitos B e T específicos aos antígenos presentes no tumor. Nesse contexto, o objetivo do presente trabalho foi construir vacinas de DNA utilizando-se os genes dos antígenos EGFRvIII, cERBB2, MAGE e GLEA de GBM e os genes das proteínas imunomoduladoras hsp65, hsp70, gp96 e gD e avaliar suas respectivas imunogenicidades. Os genes foram avaliados in silico, sintetizados in vitro e utilizados na construção das vacinas de DNA. Ferramentas de biologia molecular e o vetor pVAX foram utilizados para obtenção das vacinas. Elas foram caracterizadas por sequenciamento e western blot e utilizadas na imunização de camundongos C57BL/6. As imunizações foram realizadas com três doses em intervalos de 12 dias combinando um antígeno tumoral e uma proteína imunomoduladora na forma de vacina de DNA. A imunogenicidade foi avaliada 20 dias após a última dose. Os ensaios ex vivo foram realizados com o soro dos animais imunizados para dosagem de anticorpos específicos contra os antígenos tumorais e com as células do baço que foram re-estimuladas com as proteínas EGFRvIII, cERBB2, MAGE e GLEA para identificar a presença de células específicas aos antígenos tumorais. Como resultado, a vacina pVAXgDGLEA foi a única capaz de induzir anticorpos do subtipo IgG2a anti-GLEA. As vacinas pVAXgDGLEA, pVAXgDEGFRvIII e pVAXgDMAGE foram capazes de ativar células específicas aos antígenos que após o re-estímulo responderam rapidamente com produção de IFN-g e IL-10. A proteína imunomoduladora gD foi, portanto, capaz de ajudar na indução de um padrão de resposta Th1, específica aos antígenos de GBM, importante no combate ao tumor e a IL-10 pode favorecer e/ou balancear a resposta no cérebro que deve ser eficaz, mas não exacerbada. / Glioblastoma multiforme (GBM) is the most common form of primary brain cancer and the most severe tumour affecting glia cells. GBM is a grade IV astrocytoma known by uncontrolled proliferation, diffused infiltrate, necrosis tendency, angiogenesis, apoptosis resistance and a wide genetic heterogeneity. The standard of care consists of maximal surgical resection, followed by a combination of radiation and chemotherapy. Despite that, tumour becomes resistant to drugs used to treatment, and the patient experiences recurrence followed by death in less than 15 months after diagnosis. An alternative in GBM treatment could be immunotherapy which aims to stimulate patients immunological system in order to obtain a specific and long-term response that can protect against recurrence. One of these alternatives involves the use of DNA vaccines codifying tumoral antigens and immunomodulatory proteins that can effectively activate tumour antigen specific B and T lymphocytes. In this context, the objective of this work was the construction of DNA vaccines using GBM antigen genes (EGFRvIII, cERBB2, MAGE e GLEA) and immunomodulatory proteins (hsp65, hsp70, gp96 e gD), followed by their immunogenicity evaluation. Genes were evaluated in silico, synthesized in vitro and used in DNA vaccines construction. Molecular biology tools and the pVAX vector were used to obtain the vaccine. They were characterized by sequencing, western blot and were used in the immunization of C57BL/6 mice. Immunizations were performed in 3 doses of a DNA vaccine combining a tumoral antigen and an immunomodulatory protein at each 12 days. Immunogenicity was evaluated 20 days after the last dose. The ex vivo assays were performed with the serum of immunized animals for antibody evaluation and spleen cells were stimulated with EGFRvIII, cERBB2, MAGE e GLEA proteins to assess tumoral antigen specific cells. The pVAXgDGLEA vaccine was the only able to induce IgG2a subtype anti-GLEA antibodies. Vaccines pVAXgDGLEA, pVAXgDEGFRvIII e pVAXgDMAGE were able to activate antigen-specific cells that produced IFN-g e IL-10 quickly after reestimulation. The gD immunomodulatory protein was able to induce a Th1 immune response, specific to GBM antigens, which is important in tumor combat while IL-10 could favor and/or balance the response in brain, which should be effective but not exacerbated.

Este estudo teve por finalidade estudar os efeitos da fototerapia com laser em baixa intensidade (Low Level Laser Therapy LLLT) sobre a inflamação e reparação após lesão criogênica realizada no sitema nervoso central (SNC) de ratos. Foram realizados 3 experimentos. Em todos os experimentos foi utilizado um modelo de deformação cortical direta induzida por lesão criogênica. A LLLT foi realizada com laser de diodo em baixa intensidade emitindo no vermelho visível (InGaAlP, 660 nm) ou no infravermelho (AlGaAr, 780 nm). Os parâmetros de irradiação foram: potência de 40 mW, área do feixe de 0,04 cm2, densidades de energia de 3 J/cm2 (3 s) ou 5 J/cm2 (5 s) determinando energias por ponto de 0,12 J e 0,20 J, respectivamente. Foram realizadas 2 irradiações com intervalo de 3 h, no modo contato e em 2 pontos por lesão. No experimento 1, 50 ratos da linhagem Wistar foram utilizados para determinar os parâmetros de LLLT capazes de influenciar na dinâmica da produção de citocinas proinflamatórias (TNF-a, IL-1b, IL-6) e antiinflamatória (IL-10). As citocinas foram mensuradas pelo teste ELISA no cérebro e no sangue dos animais, 6 e 24h após a lesão. Os grupos experimentais foram: controle (não irradiado) e 4 grupos irradiados com 3 J/cm2 ou 5 J/cm2 para cada comprimento de onda (n=10 por grupo). Para os experimentos 2 e 3 foram utilizados 40 ratos (20 não irradiados controles e 20 irradiados). A LLLT foi realizada somente com o parâmetro de irradiação do laser no infravermelho e a densidade de energia de 3 J/cm2. Nestes experimentos o processo de reparação das lesões criogênicas no SNC foi acompanhado em 6 h, 1, 7 e 14 dias após a última irradiação (n=5 por grupo por tempo experimental). No experimento 2 foi realizada a análise morfométrica da região lesionada do SNC. No experimento 3 foi analisada a distribuição das células inflamatórias (linfócitos T, leucócitos e macrófagos). Os dados de cada experimento foram comparados estatísticamente por análise de variância (ANOVA) ou Kruskal-Wallis seguido dos testes de Tukey ou de Dunn, respectivamente (F=5%). O trauma criogênico foi capaz de criar lesões focais no córtex representadas por necrose, edema, hemorragia e infiltrado inflamatório. Os achados mais marcantes foram: no experimento 1 com a irradiação do laser no infravermelho e 3 J/ cm2, o TNF- a e a IL-6 se mantiveram nos mesmos níveis em 6 e 24 h, enquanto no controle houve aumento significativo. Experimento 2: as lesões não tratadas apresentaram maior perda tecidual em 6 h que as irradiadas. Experimento 3: as lesões irradiadas apresentaram menor quantidade de leucócitos e linfócitos T nas primeiras 24 h do que nas lesões controle. A quantidade de macrófagos foi similar nos dois grupos. Conclusões: Levando em consideração as condições experimentais deste estudo concluiu-se que LLLT exerce efeitos nos processos de inflamação e reparação diminuindo a concentração de citocinas próinflamatórias (TNF-F e IL-6) no sangue e mantendo a de IL-1I no cérebro. Adicionalmente, diminui a perda tecidual inicial pós- lesão criogênica e a infiltração inicial de leucócitos e linfócitos T. / This study aimed to study the effects of phototherapy with low-intensity laser (Low Level Laser Therapy - LLLT) on inflammation and repair after cryogenic injury held in central nervous system (CNS) of rats. There were 3 experiments. In all experiments a model of deformation induced by direct cortical cryogenic injury was used. The LLLT was carried out with a low intensity diode laser emitting in the visible red (InGaAlP, 660 nm) or infrared (AlGaAs, 780 nm). The irradiation parameters were: power of 40 mW, beam area of 0.04 cm2, energy densities of 3 J/cm2 (3 s) or 5 J/cm2 (5 s) providing energy per point of 0.12 J and 0.20 J, respectively. Two irradiations were performed at 3 h-intervals, in contact mode and in 2 points for lesion. In experiment 1, 50 Wistar rats were used to determine the parameters of LLLT able to influence the dynamics of production proinflammatory cytokines (TNF-, IL-1 and IL-6) and antiinflammatory cytokine (IL- 10). Cytokines were measured by ELISA in the brain and blood of animals, 6 and 24 hours after injury. The experimental groups were: control (non-irradiated) and 4 irradiated groups [3 J/cm2 and 5 J/cm2 for each wavelength (n = 10 per group)]. For experiments 2 and 3 40 rats (20 non-irradiated - controls and 20 irradiated).were used. The LLLT was performed only with the parameter of laser irradiation on the infrared and the energy density of 3 J/cm2. In these experiments, the process of repair of cryogenic injury in the CNS was followed in 6 h, 1, 7 and 14 days after the last irradiation (n = 5 per group and time trial). In experiment 2 a morphometric analysis of the injured area of the CNS was done. In experiment 3 the distribution of inflammatory cells (lymphocytes, leukocytes and macrophages) was analyzed. Data from each experiment were compared statistically by analysis of variance (ANOVA) or Kruskal-Wallis followed by tests of Tukey or Dunn, respectively ( = 5%). Cryogenic trauma was able to create focal lesions in the cortex represented by necrosis, edema, hemorrhage and inflammatory infiltrate. The most striking findings were: in experiment 1 with the laser irradiation in the infrared and 3 J/cm 2, TNF- and IL-6 remained at the same levels at 6 and 24 h, while in the control there was a significant increase. Experiment 2: untreated lesions showed greater tissue loss than irradiated lesions in 6 h. Experiment 3: lesions irradiated had fewer leukocytes and lymphocytes in the first 24 h than control lesions. The amount of macrophages was similar in both groups. Conclusions: Considering the experimental conditions of this study it was concluded that LLLT has effects in the processes of inflammation and repair by decreasing the concentration of proinflammatory cytokines (TNF- and IL-6) in blood and holding the IL-1 in the brain. Additionally, decreases the initial tissue loss after cryogenic injury and the initial infiltration of leukocytes and lymphocytes T.

Este estudo teve por finalidade estudar os efeitos da fototerapia com laser em baixa intensidade (Low Level Laser Therapy LLLT) sobre a inflamação e reparação após lesão criogênica realizada no sitema nervoso central (SNC) de ratos. Foram realizados 3 experimentos. Em todos os experimentos foi utilizado um modelo de deformação cortical direta induzida por lesão criogênica. A LLLT foi realizada com laser de diodo em baixa intensidade emitindo no vermelho visível (InGaAlP, 660 nm) ou no infravermelho (AlGaAr, 780 nm). Os parâmetros de irradiação foram: potência de 40 mW, área do feixe de 0,04 cm2, densidades de energia de 3 J/cm2 (3 s) ou 5 J/cm2 (5 s) determinando energias por ponto de 0,12 J e 0,20 J, respectivamente. Foram realizadas 2 irradiações com intervalo de 3 h, no modo contato e em 2 pontos por lesão. No experimento 1, 50 ratos da linhagem Wistar foram utilizados para determinar os parâmetros de LLLT capazes de influenciar na dinâmica da produção de citocinas proinflamatórias (TNF-a, IL-1b, IL-6) e antiinflamatória (IL-10). As citocinas foram mensuradas pelo teste ELISA no cérebro e no sangue dos animais, 6 e 24h após a lesão. Os grupos experimentais foram: controle (não irradiado) e 4 grupos irradiados com 3 J/cm2 ou 5 J/cm2 para cada comprimento de onda (n=10 por grupo). Para os experimentos 2 e 3 foram utilizados 40 ratos (20 não irradiados controles e 20 irradiados). A LLLT foi realizada somente com o parâmetro de irradiação do laser no infravermelho e a densidade de energia de 3 J/cm2. Nestes experimentos o processo de reparação das lesões criogênicas no SNC foi acompanhado em 6 h, 1, 7 e 14 dias após a última irradiação (n=5 por grupo por tempo experimental). No experimento 2 foi realizada a análise morfométrica da região lesionada do SNC. No experimento 3 foi analisada a distribuição das células inflamatórias (linfócitos T, leucócitos e macrófagos). Os dados de cada experimento foram comparados estatísticamente por análise de variância (ANOVA) ou Kruskal-Wallis seguido dos testes de Tukey ou de Dunn, respectivamente (F=5%). O trauma criogênico foi capaz de criar lesões focais no córtex representadas por necrose, edema, hemorragia e infiltrado inflamatório. Os achados mais marcantes foram: no experimento 1 com a irradiação do laser no infravermelho e 3 J/ cm2, o TNF- a e a IL-6 se mantiveram nos mesmos níveis em 6 e 24 h, enquanto no controle houve aumento significativo. Experimento 2: as lesões não tratadas apresentaram maior perda tecidual em 6 h que as irradiadas. Experimento 3: as lesões irradiadas apresentaram menor quantidade de leucócitos e linfócitos T nas primeiras 24 h do que nas lesões controle. A quantidade de macrófagos foi similar nos dois grupos. Conclusões: Levando em consideração as condições experimentais deste estudo concluiu-se que LLLT exerce efeitos nos processos de inflamação e reparação diminuindo a concentração de citocinas próinflamatórias (TNF-F e IL-6) no sangue e mantendo a de IL-1I no cérebro. Adicionalmente, diminui a perda tecidual inicial pós- lesão criogênica e a infiltração inicial de leucócitos e linfócitos T. / This study aimed to study the effects of phototherapy with low-intensity laser (Low Level Laser Therapy - LLLT) on inflammation and repair after cryogenic injury held in central nervous system (CNS) of rats. There were 3 experiments. In all experiments a model of deformation induced by direct cortical cryogenic injury was used. The LLLT was carried out with a low intensity diode laser emitting in the visible red (InGaAlP, 660 nm) or infrared (AlGaAs, 780 nm). The irradiation parameters were: power of 40 mW, beam area of 0.04 cm2, energy densities of 3 J/cm2 (3 s) or 5 J/cm2 (5 s) providing energy per point of 0.12 J and 0.20 J, respectively. Two irradiations were performed at 3 h-intervals, in contact mode and in 2 points for lesion. In experiment 1, 50 Wistar rats were used to determine the parameters of LLLT able to influence the dynamics of production proinflammatory cytokines (TNF-, IL-1 and IL-6) and antiinflammatory cytokine (IL- 10). Cytokines were measured by ELISA in the brain and blood of animals, 6 and 24 hours after injury. The experimental groups were: control (non-irradiated) and 4 irradiated groups [3 J/cm2 and 5 J/cm2 for each wavelength (n = 10 per group)]. For experiments 2 and 3 40 rats (20 non-irradiated - controls and 20 irradiated).were used. The LLLT was performed only with the parameter of laser irradiation on the infrared and the energy density of 3 J/cm2. In these experiments, the process of repair of cryogenic injury in the CNS was followed in 6 h, 1, 7 and 14 days after the last irradiation (n = 5 per group and time trial). In experiment 2 a morphometric analysis of the injured area of the CNS was done. In experiment 3 the distribution of inflammatory cells (lymphocytes, leukocytes and macrophages) was analyzed. Data from each experiment were compared statistically by analysis of variance (ANOVA) or Kruskal-Wallis followed by tests of Tukey or Dunn, respectively ( = 5%). Cryogenic trauma was able to create focal lesions in the cortex represented by necrosis, edema, hemorrhage and inflammatory infiltrate. The most striking findings were: in experiment 1 with the laser irradiation in the infrared and 3 J/cm 2, TNF- and IL-6 remained at the same levels at 6 and 24 h, while in the control there was a significant increase. Experiment 2: untreated lesions showed greater tissue loss than irradiated lesions in 6 h. Experiment 3: lesions irradiated had fewer leukocytes and lymphocytes in the first 24 h than control lesions. The amount of macrophages was similar in both groups. Conclusions: Considering the experimental conditions of this study it was concluded that LLLT has effects in the processes of inflammation and repair by decreasing the concentration of proinflammatory cytokines (TNF- and IL-6) in blood and holding the IL-1 in the brain. Additionally, decreases the initial tissue loss after cryogenic injury and the initial infiltration of leukocytes and lymphocytes T.