Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro.

Introduction: Single nucleotide variations (SNVs) are specific genetic variations that commonly occur in a population and often do not manifest phenotypically. However, depending on their location and the type of nucleotide exchanged, an SNV can alter or inhibit the function of the gene in which it occurs. Immunoglobulin G (IgG) receptor genes have exhibited several polymorphisms, including rs1801274, which is found in the FcgRIIa gene. The replacement of A with T results in a Histidine (H) to Arginine (R) substitution, altering the affinity of the IgG receptor for IgG subtypes and C-reactive protein (CRP). In this study, we analyzed rs1801274 and its functional implications concerning L. Infantum uptake and cytokine production. Methods: We genotyped 201 individuals from an endemic area for visceral leishmaniasis to assess the presence of rs1801274 using Taqman probes for a candidate gene study. Additionally, we included seventy individuals from a non-endemic area for a functional study. Subsequently, we isolated and cultivated one-week adherent mononuclear cells (AMCs) derived from the peripheral blood of participants residing in the non-endemic region in the presence of L. infantum promastigotes, with and without antigen-specific IgG and/or CRP. We analyzed the rate of phagocytosis and the production of nitric oxide (NO), tumor necrosis factor (TNF)-a, interleukin (IL)-10, IL-12 p70, IL-1b, IL- 6, and IL-8 in the culture supernatants. Results and discussion: In participants from the endemic region, the A/G (H/R isoform) heterozygous genotype was significantly associated with susceptibility to the disease. Furthermore, SNVs induced a change in the phagocytosis rate in an opsonin-dependent manner. Opsonization with IgG increased the production of IL-10, TNF-a, and IL-6 in AMCs with the H/R isoform, followed by a decrease in NO production. The results presented here suggest that the rs1801274 polymorphism is linked to a higher susceptibility to visceral leishmaniasis.

Loss of cis-PTase function in the liver promotes a highly penetrant form of fatty liver disease that rapidly transitions to hepatocellular carcinoma.

Obesity-linked fatty liver is a significant risk factor for hepatocellular carcinoma (HCC)1,2; however, the molecular mechanisms underlying the transition from non-alcoholic fatty liver disease (NAFLD) to HCC remains unclear. The present study explores the role of the endoplasmic reticulum (ER)-associated protein NgBR, an essential component of the cis-prenyltransferases (cis-PTase) enzyme3, in chronic liver disease. Here we show that genetic depletion of NgBR in hepatocytes of mice (N-LKO) intensifies triacylglycerol (TAG) accumulation, inflammatory responses, ER/oxidative stress, and liver fibrosis, ultimately resulting in HCC development with 100% penetrance after four months on a high-fat diet. Comprehensive genomic and single cell transcriptomic atlas from affected livers provides a detailed molecular analysis of the transition from liver pathophysiology to HCC development. Importantly, pharmacological inhibition of diacylglycerol acyltransferase-2 (DGAT2), a key enzyme in hepatic TAG synthesis, abrogates diet-induced liver damage and HCC burden in N-LKO mice. Overall, our findings establish NgBR/cis-PTase as a critical suppressor of NAFLD-HCC conversion and suggests that DGAT2 inhibition may serve as a promising therapeutic approach to delay HCC formation in patients with advanced non-alcoholic steatohepatitis (NASH).

A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model.

Anorexia nervosa (AN) is a psychiatric illness with the highest mortality. Current treatment options have been limited to psychotherapy and nutritional support, with low efficacy and high relapse rates. Hypothalamic AgRP (agouti-related peptide) neurons that coexpress AGRP and neuropeptide Y (NPY) play a critical role in driving feeding while also modulating other complex behaviors. We have previously reported that genetic ablation of Tet3, which encodes a member of the TET family dioxygenases, specifically in AgRP neurons in mice, activates these neurons and increases the expression of AGRP, NPY, and the vesicular GABA transporter (VGAT), leading to hyperphagia and anxiolytic effects. Bobcat339 is a synthetic small molecule predicted to bind to the catalytic pockets of TET proteins. Here, we report that Bobcat339 is effective in mitigating AN and anxiety/depressive-like behaviors using a well-established mouse model of activity-based anorexia (ABA). We show that treating mice with Bobcat339 decreases TET3 expression in AgRP neurons and activates these neurons leading to increased feeding, decreased compulsive running, and diminished lethality in the ABA model. Mechanistically, Bobcat339 induces TET3 protein degradation while simultaneously stimulating the expression of AGRP, NPY, and VGAT in a TET3-dependent manner both in mouse and human neuronal cells, demonstrating a conserved, previously unsuspected mode of action of Bobcat339. Our findings suggest that Bobcat339 may potentially be a therapeutic for anorexia nervosa and stress-related disorders.

Effects of complementary spiritual therapy on stress, anxiety, burnout syndrome and hematological parameters of professionals in a public hospital: a randomized controlled trial.

OBJECTIVES: This randomized controlled trial evaluated the stress, anxiety, and burnout of professionals exposed to complementary spiritist therapy (CST), which consists in therapeutic resources as prayer, Spiritist passe, fluidic water and spiritual education or control. METHODS: Seventy-six professionals were randomized to CST or control: to maintain the routine for 5 weeks. The ISSL scale, anxiety and depression Beck's indices, Maslach instrument, subjective well-being and WHOQOL-BREF were used at baseline and five-week. Blood count and cytokine dosage were collected at baseline, one-week and five-week. Analysis using the intention to treat approach. RESULTS: The means of variation of stress (exhaustion phase) between baseline and five-week were -1.50 ± 3.31 in the CST and 0.72 ± 3.50 in the control (p=0.036), effect size for CST group was d=0.65, which is considered medium effect. CST showed decrease in emotional exhaustion and negative affects, and increase in lymphocytes, erythrocyte parameters and platelets between the baseline and five-week (p<0.05). Reduction in IL-1ß and increase in total lymphocyte count were observed with 2-3 sessions per week, but that does not maintain when the number of sessions is decreased. Participants receiving ≥7 sessions reduced emotional exhaustion, depersonalization and stress, and improved hematological parameters throughout the study (p<0.05). CONCLUSIONS: CST may be effective in reducing stress (exhaustion phase) compared to control. Higher frequency of interventions promotes better psychic state, evidenced by large effect size for emotional exhaustion in burnout, and improves hematological parameters of professionals.

TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons.

The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide-expressing (AGRP-expressing) neurons play an essential role in driving feeding, while also modulating nonfeeding behaviors. Besides AGRP, these neurons produce neuropeptide Y (NPY) and the neurotransmitter GABA, which act in concert to stimulate food intake and decrease energy expenditure. Notably, AGRP, NPY, and GABA can also elicit anxiolytic effects. Here, we report that in adult mouse AGRP neurons, CRISPR-mediated genetic ablation of Tet3, not previously known to be involved in central control of appetite and metabolism, induced hyperphagia, obesity, and diabetes, in addition to a reduction of stress-like behaviors. TET3 deficiency activated AGRP neurons, simultaneously upregulated the expression of Agrp, Npy, and the vesicular GABA transporter Slc32a1, and impeded leptin signaling. In particular, we uncovered a dynamic association of TET3 with the Agrp promoter in response to leptin signaling, which induced 5hmC modification that was associated with a chromatin-modifying complex leading to transcription inhibition, and this regulation occurred in both the mouse models and human cells. Our results unmasked TET3 as a critical central regulator of appetite and energy metabolism and revealed its unexpected dual role in the control of feeding and other complex behaviors through AGRP neurons.

Role of Cytokines, Chemokines and IFN-γ+ IL-17+ Double-Positive CD4+ T Cells in Patients with Multiple Sclerosis.

Multiple sclerosis is mediated by self-reactive myelin T and B cells that lead to axonal and myelin damage. The immune response in multiple sclerosis involves the participation of CD4+ T cells that produce cytokines and chemokines. This participation is important to find markers for the diagnosis and progression of the disease. In our work, we evaluated the profile of cytokines and chemokines, as well as the production of double positive CD4+ T cells for the production of IFNγ IL-17 in patients with multiple sclerosis, at different stages of the disease and undergoing different treatments. We found that relapsing-remitting patients had a significant increase in IL-12 production. About IL-5, its production showed significantly higher levels in secondarily progressive patients when compared to relapsing-remitting patients. IFN-γ production by PBMCs from secondarily progressive patients showed significantly higher levels. This group also had a higher percentage of CD4+ IFNγ+ IL-17+ T cells. The combination of changes in certain cytokines and chemokines together with the presence of IFNγ+ IL-17+ double positive lymphocytes can be used to better understand the clinical forms of the disease and its progression.

Hemolymph of triatomines presents fungistatic activity against Cryptococcus neoformans and improves macrophage function through MCP-I/TNF-α increase.

Background: Triatomines are blood-feeding arthropods belonging to the subfamily Triatominae (Hemiptera; Reduviidae), capable of producing immunomodulatory and water-soluble molecules in their hemolymph, such as antimicrobial peptides (AMPs). In this work, we evaluated the antifungal and immunomodulatory activity of the hemolymph of Meccus pallidipennis (MPH) and Rhodnius prolixus (RPH) against Cryptococcus neoformans. Methods: We assessed the activity of the hemolymph of both insects on fungal growth by a minimum inhibitory concentration (MIC) assay. Further, RAW 264.7 macrophages were cultivated with hemolymph and challenged with C. neoformans. Then, their phagocytic and killing activities were assessed. The cytokines MCP-1, IFN-γ, TNF-α, IL-10, IL-12, and IL-6 were measured in culture supernatants 4- and 48-hours post-infection. Results: Both hemolymph samples directly affected the growth rate of the fungus in a dose-dependent manner. Either MPH or RPH was capable of inhibiting fungal growth by at least 70%, using the lowest dilution (1:20). Treatment of RAW 264.7 macrophages with hemolymph of both insects was capable of increasing the production of MCP-I and TNF-α. In addition, when these cells were stimulated with hemolymph in the presence of C. neoformans, a 2- and a 4-fold increase in phagocytic rate was observed with MPH and RPH, respectively, when compared to untreated cells. For the macrophage killing activity, MPH decreased in approximately 30% the number of viable yeasts inside the cells compared to untreated control; however, treatment with RPH could not reduce the total number of viable yeasts. MPH was also capable of increasing MHC-II expression on macrophages. Regarding the cytokine production, MCP-I and TNF-α, were increased in the supernatant of macrophages treated with both hemolymphs, 4 and 48 hours after stimulation. Conclusion: These results suggested that hemolymph of triatomines may represent a source of molecules capable of presenting antifungal and immunomodulatory activity in macrophages during fungal infection.

Hemolymph of triatomines presents fungistatic activity against Cryptococcus neoformans and improves macrophage function through MCP-I/TNF-α increase

Triatomines are blood-feeding arthropods belonging to the subfamily Triatominae (Hemiptera; Reduviidae), capable of producing immunomodulatory and water-soluble molecules in their hemolymph, such as antimicrobial peptides (AMPs). In this work, we evaluated the antifungal and immunomodulatory activity of the hemolymph of Meccus pallidipennis (MPH) and Rhodnius prolixus (RPH) against Cryptococcus neoformans. Methods: We assessed the activity of the hemolymph of both insects on fungal growth by a minimum inhibitory concentration (MIC) assay. Further, RAW 264.7 macrophages were cultivated with hemolymph and challenged with C. neoformans. Then, their phagocytic and killing activities were assessed. The cytokines MCP-1, IFN-γ, TNF-α, IL-10, IL-12, and IL-6 were measured in culture supernatants 4- and 48-hours post-infection. Results: Both hemolymph samples directly affected the growth rate of the fungus in a dose-dependent manner. Either MPH or RPH was capable of inhibiting fungal growth by at least 70%, using the lowest dilution (1:20). Treatment of RAW 264.7 macrophages with hemolymph of both insects was capable of increasing the production of MCP-I and TNF-α. In addition, when these cells were stimulated with hemolymph in the presence of C. neoformans, a 2- and a 4-fold increase in phagocytic rate was observed with MPH and RPH, respectively, when compared to untreated cells. For the macrophage killing activity, MPH decreased in approximately 30% the number of viable yeasts inside the cells compared to untreated control; however, treatment with RPH could not reduce the total number of viable yeasts. MPH was also capable of increasing MHC-II expression on macrophages. Regarding the cytokine production, MCP-I and TNF-α, were increased in the supernatant of macrophages treated with both hemolymphs, 4 and 48 hours after stimulation. Conclusion: These results suggested that hemolymph of triatomines may represent a source of molecules capable of presenting antifungal and immunomodulatory activity in macrophages during fungal infection.(AU)

Application of physical exercise therapies in breast cancer survivors and their effects on the inflammatory profile: A narrative review.

BACKGROUND: One of the adverse effects of cancer treatments is the exacerbation of inflammation, which generates numerous limitations and contributes to the development of several comorbidities and the recurrence of cancer itself. Physical exercise (PE) has been proposed as an efficient complementary strategy to combat the inflammatory effects of oncological treatments and to prevent the development of comorbidities, but its adequate application in breast cancer survivors (BCS) requires the establishment of consensuses and practical recommendations. OBJECTIVE: This study aimed to review the randomized controlled trials that evaluated the influence of PE in the inflammatory profile of BCS. METHODS: The search for articles published between 1999 and 2020 was done in PsycINFO, PubMed, Cochrane, Science Direct, and Scopus databases. RESULTS: Current knowledge reveals the effectiveness of PE in the functional independence and health of BCS. Evidence of the capacity of PE to improve the inflammatory profile and the immune response in BCS has also been described. However, the heterogeneity of the studies regarding structural training variables, types of exercise, stages of intervention, and severity of the disease, still do not allow the establishment of precise guidelines for the prescription and progression of exercise to improve the inflammatory process in BCS. DISCUSSION: . This review suggests a possible strategy to be used in the assessment, training prescription, and rehabilitation of BCS, to support the development of new studies and the work of exercise professionals in the prescription and application of physical training to improve health and inflammatory status in BCS.

Religiosidade/espiritualidade, indicadores de saúde mental e parâmetros hematológicos de profissio-nais de enfermagem / Religiosity/spirituality, mental health indicators and hematologic parameters of nursing professionals / Religiosidad/espiritualidad, indicadores de salud mental y parámetros hematológicos de profesionales de enfermeiras

Objetivo:analisara relação entre Religiosidade e Espiritualidade,indicadores de saúde mental, parâmetros hematológicos e percepção dasaúde de profissionais deenfermagem.Método:estudo transversal com 53 funcionários. Utilizou-se Medida Multidimensional Breve de Religiosidade e Espiritualidade, Inventário Stress Lipp,Ansiedade e Depressão de Beck, Bem-Estar Subjetivo,hemograma e imunoglobulina A. Resultados:Dimensões Experiências Espirituais Diárias eAutoavaliação Global são os fatores commaior forçade relação com os índices de estresse, depressão e Bem-Estar em profissionais.Participação religiosa e comprometimento foramosfatores que influenciarammaiores valores de leucócitos,neutrófilose imunoglobulina A. Conclusão:os resultados identificaram relação entre Religiosidade e Espiritualidade, indicadores de saúde mental e parâmetros hematológicos. Profissionais de enfermagemmais religiosos e espiritualistas apresentam melhor saúde mental e maior imunidade, além de melhor percepção de saúde (AU).

Objective:to analyze the relationship between Religiosity and Spirituality, mental health indicators and haematological parameters of nurses. Method:cross-sectional study with 53 employees. It was used Brief Multidimensional Measure of Religiosity and Spirituality (BMMRS), Lipp Stress Inventory, Beck Anxiety and Depression and Subjective Wellbeing, hemogram and immunoglobulin A. Results:dimensions Daily Spiritual Experiences and Global Religiosity and Spirituality Self-evaluation are the factors that present greater strength of relation with the indices of stress, depression and Subjective Wellbeing in professionals. Religious participation and impairment were the factors that influenced higher leukocyte, neutrophil and immunoglobulin A values.Conclusion:the results identified a relation between Religiosity and Spirituality, mental health indicators and haematological parameters, demonstrating that more religious and spiritualist nurses have better mental health and immunity,as well as a better perception of health (AU).

Objetivo:analizar la relación entre Religiosidad y Espiritualidad, indicadores de salud mental y parámetros hematológicos de enfermeras. Método:estudio transversal con 53 empleados. Se utilizó Medida Multidimensional Breve de Religiosidad y Espiritualidad (BMMRS), Inventario Stress Lipp, Escalas de Ansiedad y Depresión Beck y Bienestar Subjetivo, cuestionario de clasificación de la salud,hemograma yinmunoglobulina A. Resultados:las dimensiones Experiencias Espirituales Diarias y Autoevaluación Global de Religiosidad y Espiritualidad son los factores que presentan mayor fuerza de relación con los índices de estrés, depresión y Bienestar Subjetivo en profesionales. La participación religiosa y compromiso fueron los principales factores que influyen en los valores de leucocitos, neutrófilos, y la inmunoglobulina A. Conclusión:los resultados identificaron relación entre R/E, indicadores de salud mental y parámetros hematológicos, demostrandoque enfermeras más religiosos y espiritualistas presentan mejor salud mental y mayor inmunidad, además de una mejor percepción de la salud (AU).

Metabolism: A Burning Opioid Issue in Obesity Therapeutics.

Food restriction triggers a lowering in body temperature. A new study now provides a mechanism for this process that relies on opioid signaling in the hypothalamus. These observations suggest potential new therapeutics for obesity.

Nanoparticle-Mediated Drug Delivery: Blood-Brain Barrier as the Main Obstacle to Treating Infectious Diseases in CNS.

BACKGROUND: Parasitic infections affecting the central nervous system (CNS) present high morbidity and mortality rates and affect millions of people worldwide. The most important parasites affecting the CNS are protozoans (Plasmodium sp., Toxoplasma gondii, Trypanosoma brucei), cestodes (Taenia solium) and free-living amoebae (Acantamoeba spp., Balamuthia mandrillaris and Naegleria fowleri). Current therapeutic regimens include the use of traditional chemicals or natural compounds that have very limited access to the CNS, despite their elevated toxicity to the host. Improvements are needed in drug administration and formulations to treat these infections and to allow the drug to cross the blood-brain barrier (BBB). METHODS: This work aims to elucidate the recent advancements in the use of nanoparticles as nanoscaled drug delivery systems (NDDS) for treating and controlling the parasitic infections that affect the CNS, addressing not only the nature and composition of the polymer chosen, but also the mechanisms by which these nanoparticles may cross the BBB and reach the infected tissue. RESULTS: There is a strong evidence in the literature demonstrating the potential usefulness of polymeric nanoparticles as functional carriers of drugs to the CNS. Some of them demonstrated the mechanisms by which drugloaded nanoparticles access the CNS and control the infection by using in vivo models, while others only describe the pharmacological ability of these particles to be utilized in in vitro environments. CONCLUSION: The scarcity of the studies trying to elucidate the compatibility as well as the exact mechanisms by which NDDS might be entering the CNS infected by parasites reveals new possibilities for further exploratory projects. There is an urgent need for new investments and motivations for applying nanotechnology to control parasitic infectious diseases worldwide.

Pemphigus foliaceus patients (Fogo Selvagem) treated with kinesiotherapy presented lower levels of proinflammatory cytokines.

Fogo Selvagem (FS) is a rare autoimmune disease characterized by acantholysis and inflammation of the epidermis. It was evidenced in this disease the increase of proinflammatory cytokines levels which can be influenced by physical activities. Kinesiotherapy, as physiotherapeutic interventions, was associated improvement levels of the quality of live, mainly the pain. Understanding the impact of such methodology in immunology of the FS, may constitute an alternative and effective approach. We compare the levels of serum cytokines and chemokines between nine patients with FS submitted to kinesiotherapy for 12 weeks and ten patients not submitted to kinesiotherapy. The kinesiotherapy was composed by self-stretching followed by a resistance training for upper and lower limbs. The protocol was carried out in three sections of eight to ten repetitions with 70% of the maximum load measured by test maximum of ten repetitions. After strengthening period patients performed a passive stretching. The training sessions lasted 50 min and were performed 3 times a week at least 12 weeks. Cytokines and chemokines were assessed in plasma using enzyme-linked immunosorbent assay and/or cytometric bead array. Patients with FS were being kinesiotherapy presented minors levels of interferon-γ, interleukin (IL)-17, IL-22, and IL-15 when compared to those not submitted to kinesiotherapy. No differences were observed for the detection of the chemokines chemokine ligand (CCL)-2, CCL-3, CCL-5, CCL-11, C-X-C motif chemokine 8 (CXCL-8), and CXCL-10. These results suggest that kinesiotherapy had a positive impact on inflammatory markers that are associated with disease worsening in FS.

Th1, Th17, and Treg Responses are Differently Modulated by TNF-α Inhibitors and Methotrexate in Psoriasis Patients.

Psoriasis is a chronic, recurrent, immune-mediated, hyperproliferative inflammatory skin disease. The role of the adaptive immune system, particularly of Th1 and Th17 lymphocytes, has been regarded as prominent in the immunopathogenesis of psoriasis, as well as decreased Tregs function. Immunobiological drugs were administered in therapeutic pulses and a few studies evaluate their effects on the immune repertoire. The aim of this study was to evaluate the adaptive immune profile of patients with severe psoriasis under immunobiological treatment in two time points. Thirty-two psoriasis patients and 10 control patients were evaluated. In the group of psoriasis patients, 10 patients were on anti-TNF and 14 patients on methotrexate treatment, while 8 individuals were not treated. IL-17, IFN-γ, TNF-α, IL-6, IL-2, and IL-10 were analyzed. CD4 T cell intracellular cytokines were analyzed. It was observed that stimulation could significantly increase the production of IL-17, IFN-γ, TNF-α, and IL-10 only before anti-TNF pulse therapy. The activation of Th1 and Treg cells after stimulation was significantly higher before anti-TNF pulse. Patients on methotrexate or anti-TNF therapy produced significantly lower levels of TNF-α, IL-10, and IL-6. Furthermore, these patients showed a significant decrease in the activated CD4+ T cells. The treatment with immunomodulator or methotrexate modulates the activation of CD4+ T cells, and anti-TNF treatment appears to have a modulating effect on the activation and production of Th1, Th17, and Treg cells.

Salivary Gland Extract of Kissing Bug, Triatoma lecticularia, Reduces the Severity of Intestinal Inflammation through the Modulation of the Local IL-6/IL-10 Axis.

Triatomines are known for their role as vectors of the causative agent of Chagas disease. The occurrence of an arsenal of molecules in their saliva is able to suppress vertebrate immune responses. Thus, it is reasonable to assume that the presence of molecules with therapeutic potential in their saliva is able to constrain inflammation in immune-mediated diseases. Thus, mice were exposed to dextran sulfate sodium (DSS) in drinking water uninterruptedly during 6 consecutive days and treated with T. lecticularia salivary gland extract (SGE) (3, 10, or 30 µg) or vehicle (saline) (n = 6/group). At the highest dose (30 µg), an improvement in clinical outcome and macroscopic aspects of the intestine were observed. This observation was followed by amelioration in histopathological aspects in the colon especially when the doses of 10 and 30 µg were used. Regardless of the concentration used, treatment with T. lecticularia SGE significantly reduced the levels of the inflammatory cytokine IL-6 in the intestine. The production of the anti-inflammatory cytokine IL-10 was positively impacted by the concentrations of 3 and 30 µg. Our results suggest that the presence of molecules in the T. lecticularia SGE is able to attenuate clinical outcome and colon shortening and improve intestinal architecture besides reducing the production of IL-6 and inducing a local production of IL-10 in the intestine.

TNF-α blockade impairs in vitro tuberculous granuloma formation and down modulate Th1, Th17 and Treg cytokines.

Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients. We evaluated 76 individuals, with tuberculosis active, treated and subjects with positive PPD. Granuloma formation was induced in the presence or absence of Infliximab for up to 10 days. The use of Infliximab in cultures significantly blocked TNF-α production (p <0.05), and led to significant changes in granuloma structure, in vitro, only in the treated TB group. On the other hand, there was a significant reduction in the levels of IFN-γ, IL-12p40, IL-10 and IL-17 after TNF-α blockade in the three experimental groups (p <0.05). Taken together, our results demonstrate that TNF-α blockade by Infliximab directly influenced the structure of granuloma only in the treated TB group, but negatively modulated the production of Th1, Th17 and regulatory T cytokines in the three groups analyzed.

Cytokine and Chemokines Alterations in the Endemic Form of Pemphigus Foliaceus (Fogo Selvagem).

INTRODUCTION: The endemic form (fogo selvagem-FS) of pemphigus foliaceus is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-1. Despite the array of findings, the role of chemokines and cytokines that dictate the immune response and disease outcome is still poorly investigated. MATERIALS AND METHODS: Serum from 64 patients diagnosed with FS was used to draw and establish the levels of these molecules on this disease and establish the levels of these molecules with the severity of FS, and influence of treatment. RESULTS: In comparison to healthy subjects, FS patients, newly diagnosed and still without therapeutic intervention, had higher levels of IL-22 and CXCL-8, and reduced levels of IFN-γ, IL-2, IL-15, and CCL-11. Furthermore, treatment using immunosuppressant drugs augmented the production of IFN-γ, IL-2, CCL-5, and CCL-11 besides reducing the levels of IL-22 and CXCL-10. Immunosuppressive therapy seemed to have long-lasting effects on the production of higher amounts of IFN-γ, IL-2, and CCL-5, besides keeping lowered the levels of IL-22 in remission FS patients. CONCLUSION: Taken together, our findings suggest a putative role of IL-22 in the pathogenesis of FS. Finally, data presented here may contribute for better understanding the immune aspects that control disease outcome.

Th1/Th17-Related Cytokines and Chemokines and Their Implications in the Pathogenesis of Pemphigus Vulgaris.

Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-3. Despite the variety of findings, the chemokine and cytokine profiles that characterize the immune response in the disease are still poorly explored. Thus, 20 PV patients and 20 controls were grouped according to gender, ethnicity, place of residence, and clinical parameters of the disease. Then, the levels of chemokines and of Th1/Th2/Th17/Treg/Th9/Th22-related cytokines were assessed in the serum. PV patients had higher levels of inflammatory Th1/Th17 cytokines (IFN-γ, IL-17, and IL-23), as well as higher levels of CXCL8 and reduced levels of Th1/Th2-related chemokines (IP-10 and CCL11). However, no differences in the levels of IL-2, IL-6, TNF-α, IL-1ß, IL-4, IL-9, IL-12, TGF-ß, IL-33, MCP-1, RANTES, and MIP-1α were found between PV patients and their control counterparts. Furthermore, PV patients with skin lesions had higher serum levels of IL-6 and CXCL8 when compared to PV patients without lesions. Taken together, our findings describe the role of cytokines and chemokines associated with Th1/Th17 immune response in PV patients. Finally, these data are important for better understanding of the immune aspects that control disease outcome, and they may also provide important information about why patients develop autoantibodies against desmogleins.