Repositório Institucional - Unifesp :: Navegando por Palavras-chave "cytokine"

Navegando por Palavras-chave "cytokine"

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Cytokine Alterations in Bipolar Disorder: A Meta-Analysis of 30 Studies
(Elsevier B.V., 2013-07-01) Modabbernia, Amirhossein; Taslimi, Shervin; Brietzke, Elisa [UNIFESP]; Ashrafi, Mandana; Univ Tehran Med Sci; Universidade Federal de São Paulo (UNIFESP)
Background: We conducted a meta-analysis of studies comparing cytokine concentrations between patients with bipolar disorder (BD) and healthy control subjects (HCs).Methods: We searched ISI Web of Science, MEDLINE, BIOSIS Previews, Scopus, Current Contents Connect, and Biological Abstracts for relevant studies. Based on heterogeneity status, we used fixed-effect or restricted maximal likelihood model to perform meta-analysis.Results: Thirty studies with a total of 2599 participants (1351 BD and 1248 HCs) were eligible for the analysis. Concentrations of interleukin (IL)-4 (p = .008), IL-6 (p = .073), IL-10 (p = .013), soluble IL-2 receptor (sIL-2R; p < .001), sIL-6R (p = .021), tumor necrosis factor (TNF)-alpha (p = .010), soluble TNF receptor-1 (sTNFR1; p < .001), and IL-1 receptor antagonist (p value in mania <.001 and euthymia = .021) were significantly elevated in patients compared with HCs. Moreover, IL-1 beta (p = .059), and IL-6 (p = .073) tended to show higher values in patients. Levels of IL-2 (p = .156), interferon (INF)-gamma (p = .741), C-C motif ligand 2 (p = .624), and IL-8 (p = .952) did not significantly differ between patients and HCs. Subgroup analysis based on mitogen stimulation status partially or completely resolved heterogeneity for most of the cytokines. Concentrations of IL-2, IL-4, sIL-6R, and INF-gamma were unrelated to medication status. Phasic difference was present for TNF-alpha, sTNFR1, sIL-2R, IL-6, and IL-1RA, whereas it was absent for IL-4 and IL-10.Conclusions: This meta-analysis provides evidence for significant elevation of proinflammatory, anti-inflammatory, and regulatory cytokines in BD.
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Effect of microcystin on leukocyte viability and function
(Elsevier B.V., 2006-06-01) Goncalves, EAP; Dalboni, Maria Aparecida [UNIFESP]; Peres, A. T.; Manfredi, A. P.; Manfredi, SR; Azevedo, S. M.; Magalhaes, V. F.; Draibe, S.; Canziani, MEF; Cendoroglo, M.; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Rio de Janeiro (UFRJ)
Microcystin (MC) has been found in several areas of the world. in addition to its hepatotoxicity, microcystin may have an immunomodulatory effect.Considering that patients receiving hemodialysis may be chronically exposed to variable concentrations of MC, and that they present important changes in this immune response, we have assessed the effect of MC on the function of leukocytes.Polymorphonuclear leukocytes isolated from health), volunteers (HV) and patients receiving hemodialysis (HD) were incubated with microcystin (10 mu g/L) for 24 h and evaluated for reactive oxygen species production (ROS), phagocytosis and apoptosis. Monocytes incubated with and without LPS (100 ng/mL) and microcystin for 24 h were assessed for TNF alpha and IL10 production.Leukocytes of HV presented an increase in apoptosis rates and leukocytes from HD exhibited a lower production of oxygen-reactive species, both spontaneously and after stimulus with S. aureus, when compared with leukocytes incubated without toxin.Monocytes presented an increase in cytokine production after stimulation by LPS in both groups, but there was no difference between the groups with and without MC that were incubated with or without LPS.Low concentrations of microcystin can induce mild changes in leukocyte function of HV and HDP, particularly in the ability to produce ROS. (c) 2006 Elsevier B.V. All rights reserved.
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Evaluating budesonide efficacy in nasal polyposis and predicting the resistance to treatment
(Wiley-Blackwell, 2009-01-01) Valera, F. C. P.; Queiroz, R.; Scrideli, C.; Tone, L. G.; Anselmo-Lima, W. T.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
Cell resistance to glucocorticoids is a major problem in the treatment of nasal polyposis (NP).The objectives of this study were to observe the effect of budesonide on the expression of IL-1 beta, TNF-alpha, granulocyte macrophage-colony stimulating factor, intercellular adhesion molecule (ICAM)-1, basic fibroblast growth factor, eotaxin-2, glucocorticoid receptor (GR)-alpha, GR-beta, c-Fos and p65 in nasal polyps and to correlate their expression to clinical response.Biopsies from nasal polyps were obtained from 20 patients before and after treatment with topical budesonide. Clinical response to treatment was monitored by a questionnaire and nasal endoscopy. the mRNA levels of the studied genes were measured by real-time quantitative (RQ)-PCR.There was a significant decrease in the expression of TNF-alpha (P < 0.05), eotaxin-2 (P < 0.05) and p65 (P < 0.05) in NP after treatment. Poor responders to glucocorticoids showed higher expression of IL-1 beta (3.74 vs. 0.14; P < 0.005), ICAM-1 (1.91 vs. 0.29; P < 0.05) and p65 (0.70 vs. 0.16; P < 0.05) before treatment. Following treatment, IL-1 beta (4.18 vs. 0.42; P < 0.005) and GR-beta (0.95 vs. 0.28; P < 0.05) mRNA expression was higher in this group.Topical budesonide reduced the expression of TNF-alpha, eotaxin-2 and p65. Poor responders to topical budesonide exhibit higher levels of IL-1 beta, ICAM-1 and nuclear factor (NF)-kappa B at diagnosis and higher expression of both IL-1 beta and GR-beta after treatment. These results emphasize the anti-inflammatory action of topical budesonide at the molecular level and its importance in the treatment of NP. Nevertheless, IL-1 beta, ICAM-1 and NF-kappa B may be associated with primary resistance to glucocorticoids in NP, whereas higher expression of GR-beta in poor responders only after glucocorticoid treatment may represent a secondary drug resistance mechanism in this disease.
Acesso aberto (Open Access)
Evidence for Involvement of IL-9 and IL-22 in Cows' Milk Allergy in Infants
(Mdpi Ag, 2017) Barros, Karina V. [UNIFESP]; Flor Silveira, Vera L. [UNIFESP; Laranjeira, Marisa S.; Wandalsen, Neusa F.; Passeti, Susana; De Oliveira, Roberta; Munekata, Regina V.; Noakes, Paul S.; Miles, Elizabeth A.; Calder, Philip C.
Although allergic inflammation is characterized by a T helper (Th) 2-dominant immune response, the discovery of a role for new T cell subsets in inflammatory diseases has added an additional layer of complexity to the understanding of the pathogeneses of allergic diseases. We evaluated plasma cytokine profiles in infants with cows' milk allergy (CMA), who were being treated with an elimination diet. In a prospective, randomized and controlled study, infants (aged 8.4 +/- 3.9 months) with CMA were treated with an elimination diet for 120 days, which replaced cows' milk with a hydrolysed soy protein formula (n = 26) or a free amino acid formula (n = 20). Blood samples were collected before treatment during active disease (T0) and after 120 days, when symptoms were absent (T1). Plasma cytokine concentrations were measured. Infants with CMA had higher plasma concentrations of interleukin (IL)-4 and IL-13 and lower concentrations of IL-9, IL-17A and interferon-gamma, compared with healthy breast-fed infants. At T0, there was a positive correlation between blood eosinophil numbers and plasma concentrations of IL-4, IL-9, IL-17A and IL-22. Treatment with a cows' milk elimination diet resulted in a decrease in plasma IL-4, IL-9, IL-13 and IL-22 and an increase in plasma IL-17A. We conclude that IL-4 and IL-13 are elevated in active CMA. The association of IL-9 and IL-22 with eosinophilia, and the decrease in these two cytokines with cows' milk elimination, suggests that they both play a role in the symptoms observed in CMA and may be important targets for future interventions.
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Genetic Polymorphisms and Recurrent Spontaneous Abortions: An Overview of Current Knowledge
(Wiley-Blackwell, 2012-04-01) Daher, Silvia [UNIFESP]; Mattar, Rosiane [UNIFESP]; Gueuvoghlanian-Silva, Barbara Y. [UNIFESP]; Torloni, Maria R. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
The relevance of gene polymorphisms in the development of unexplained recurrent spontaneous abortion is still unclear. Cytokines, angiogenic mediators, and hormones are involved in all stages of reproduction and pregnancy outcome. Impaired production and/or unbalanced ratios of these mediators have been implicated in the pathogenesis of unexplained recurrent spontaneous abortion. Functional polymorphism influence gene activity and therefore can interfere with the expression of mediators. Several studies have been carried out to evaluate the relationship between cytokines, angiogenic mediators, and hormones gene polymorphisms and unexplained recurrent spontaneous abortion. the results of these studies are mostly contradictory, and few significant associations have been identified. Up to present time, the evidence is insufficient to support the evaluation of cytokines, angiogenic mediators, and hormones gene polymorphism in routine workup in all cases of recurrent pregnancy loss, and these tests are not included in any of the major obstetric guidelines.
Acesso aberto (Open Access)
Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment
(Frontiers Media Sa, 2016) Maza, Paloma Korehisa [UNIFESP]; Suzuki, Erika [UNIFESP]
Histoplasma capsulatum var. capsulatum is a dimorphic fungus that causes histoplasmosis, a human systemic mycosis with worldwide distribution. In the present work, we demonstrate that H. capsulatum yeasts are able to induce cytokine secretion by the human lung epithelial cell line A549 in integrin- and Src-family kinase (SFK)-dependent manners. This conclusion is supported by small interfering RNA (siRNA) directed to alpha 3 and alpha 5 integrins, and PP2, an inhibitor of SFK activation. siRNA and PP2 reduced IL-6 and IL-8 secretion in H. capsulatum-infected A549 cell cultures. In addition, alpha 3 and alpha 5 integrins from A549 cells were capable of associating with H. capsulatum yeasts, and this fungus promotes recruitment of these integrins and SFKs to A549 cell membrane rafts. Corroborating this finding, membrane raft disruption with the cholesterol-chelator methyl-beta-cyclodextrin reduced the levels of integrins and SFKs in these cell membrane domains. Finally, pretreatment of A549 cells with the cholesterol binding compound, and also a membrane raft disruptor, filipin, significantly reduced IL-6 and IL-8 levels in A549-H.capsulatum cultures. Taken together, these results indicate that H. capsulatum yeasts induce secretion of IL-6 and IL-8 in human lung epithelial cells by interacting with alpha 3 and alpha 5 integrins, recruiting these integrins to membrane rafts, and promoting SFK activation.
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Hypogammaglobulinemia in children: a warning sign to look deeply?
(Wiley, 2017) de Melo, Karina Mescouto [UNIFESP]; de Moraes-Pinto, Maria Isabel [UNIFESP]; Andrade, Luis E. C. [UNIFESP]; Salomao, Reinaldo [UNIFESP]; Brunialti, Milena K. C. [UNIFESP]; Ferreira, Vanessa S. [UNIFESP]; Costa-Carvalho, Beatriz T. [UNIFESP]
This study investigated phenotypic and functional characteristics of lymphocytes in children with common variable immunodeficiency (CVID) and unclassified hypogammaglobulinemia (UH), as well as B-cell subsets in non-consanguineous parents. Blood samples of 30 children, CVID (n = 9), UH (n = 9), healthy donors HD (n = 12), and 19 adults (parents and controls) were labeled by a combination of surface markers to identify CD4, CD8 T-cell and B-cell sub-populations. T-cell cytokine production in children was analyzed in vitro after stimulation with phytohemagglutinin (PHA) and tetanus toxoid. We observed low percentages of switched memory B cells in children with CVID, increase in total CD4(+) T-cell counts, and high percentages of transitional B cells only in UH group. Analysis of T-cell immunity showed that CVID children had decreased percentages of CD8(+) IFN-gamma-producing cells after stimulation with PHA and tetanus toxoid. Parent of children with CVID had low percentages of naive B cell and increased percentages of memory B cells in comparison with controls. These results suggest that (i) early combined immune defect in children with CVID and (ii) a possible familial B-cell disturbance in pediatric CVID.
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IL-12 inhibits endotoxin-induced inflammation in the eye
(Vch Publishers Inc, 1996-05-01) Whitcup, S. M.; Rizzo, L. V.; Lai, J. C.; Hayashi, S.; Gazzinelli, R.; Chan, C. C.; NIH; Universidade Federal de São Paulo (UNIFESP); NIAID; Universidade Federal de Minas Gerais (UFMG)
Interleukin-12 (IL-12) is a heterodimeric cytokine that induces interferon (IFN)-gamma production and an increased generation of Th 1 cells. Both IL-12 and IL-12 antagonists are being studied for the treatment of allergic reactions, autoimmune disease and malignancy. the goal of the present experiments was to examine the importance of IL-12 in endotoxin-induced ocular inflammation. the number of inflammatory cells infiltrating eyes with endotoxin-induced uveitis (EIU) was significantly increased in animals treated with intraperitoneal anti-IL-12 antibody when compared to control animals, but there was no difference in infiltrating inflammatory cells in the eyes of animals treated with IL-12 when compared to controls. in contrast, intraocular injection of IL-12 significantly inhibited the development of endotoxin-induced intraocular inflammation. the inflammatory cells were reduced in the eves of animals receiving intraocular IL-obtained from eyes with EIU showed increased levels of IFN-gamma and decreased levels of IL-6 in eyes receiving intraocular IL-12. These data show that IL-12 has an inhibitory effect on endotoxin-induced inflammation in the eye and su that IL-12 can have an immunoregulatory function in some forms of inflammatory disease.
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Impaired Treg and NK cells profile in overweight women with gestational diabetes mellitus
(Wiley, 2018) Lobo, Thalita Frutuoso [UNIFESP]; Borges, Cannila de Moraes [UNIFESP]; Mattar, Rosiane [UNIFESP]; Gomes, Caio Perez [UNIFESP]; Angelo, Ana Geisa Santos de [UNIFESP]; Pendeloski, Karen Priscilla Tezotto [UNIFESP]; Daher, Silvia [UNIFESP]
Problem: Maternal obesity is frequently associated with gestational diabetes mellitus (GDM), and immunological mechanisms seem to be involved in the physiopathology of these conditions. The aim of this study was to characterize the profile of immune cells in peripheral blood of overweight women with GDM. Method of Study: This case-control study included 27 glucose-tolerant (controls) and 31 GDM overweight pregnant women. Flow cytometry was used to assess the number of regulatory T cells (Treg) and natural killer (NK) cells in the peripheral blood. In addition, the expression of IL-10, TGF-B, and TNF-A in Treg and expression of IFN-G, TNF-A, granzyme, and perforin in NK cells were analyzed. Results: GDM patients had significantly lower frequency of TCD4(+)CD25(bright) and TCD4(+)CD25(+)FOXP3(high) cells, higher production of TNF-A by Treg cells and higher percentage of NKCD16(+)56(dim) cells than the controls. Conclusion: The association between obesity and GDM is a condition where it is observed impaired Treg and NK cells profile, findings that seem to be related with the development of IR and inflammation.
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Maternal obesity and inflammatory mediators: A controversial association
(Wiley, 2017) Pendeloski, Karen Priscilla Tezotto [UNIFESP]; Ono, Erika [UNIFESP]; Torloni, Maria ReginaV; Mattar, RosianeV [UNIFESP]; Daher, Silvia [UNIFESP]
The link between maternal obesity and inflammatory mediators is still unclear. Our aim was to summarize the main findings of recently published studies on this topic. We performed a search in Medline for studies published in the last years on obesity, human pregnancy, and inflammatory mediators. We report the findings of 30 studies. The characteristics and number of participants, study design, gestational age at sample collection, and type of sample varied widely. Approximately two-thirds of them investigated more than one mediator, and 50% included participants in only one trimester of pregnancy. The most frequently investigated mediators were leptin, tumour necrosis factor-alpha (TNF-alpha), and interleukin (IL)-6. Almost all studies reported an association between maternal obesity, leptin, and C-reactive protein (CRP) serum levels but not with IL-1 beta and IL-10. The association of IL-6, TNF-alpha, monocyte chemo-attractant protein-1 (MCP-1), adiponectin, and resistin with maternal obesity is still controversial. To clarify the physiopathological link between maternal obesity and inflammation, more high-quality studies are needed.
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Regulation mechanisms of retinal pigment epithelial cell migration by the TGF-beta superfamily
(Blackwell Munksgaard, 2003-12-01) Mitsuhiro, Marcia Regina Kimie Higashi [UNIFESP]; Eguchi, S.; Yamashita, H.; Universidade Federal de São Paulo (UNIFESP); Yamagata Univ
Purpose: To investigate the expression of specific receptors, signal transducers and the effect of transforming growth factor-beta(TGF-beta) on retinal pigment epithelium (RPE) migration and proliferation.Methods: Human RPE cell line D407 was used in all experiments. the effect of TGF-beta on migration and proliferation were studied using a wound healing model and [H-3]-thymidine incorporation, respectively. the expression of RNA related to the TGF-beta superfamily receptors and SMAD1-4 were assayed by reverse transcriptase-polymerase chain reaction (RT-CPR). the effects of TGF-beta on the intracellular position of SMAD were studied by immunoperoxidase and immunofluorescence.Results: Transforming growth factor-beta 4 nM and activin A 0.36 nM stimulated RPE migration. There was no effect on proliferation. RNA for TGF-beta receptors types 1 and 2, and SMAD1-4 were detected in RPE culture. Transforming growth factor-beta signal transducer SMAD2 but not SMAD1 moved from the cytoplasm to the nucleus after TGF-beta stimulation.Conclusion: Transforming growth factor-beta can regulate RPE cell migration through specific signal transduction pathways.
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Regulation of gene expression in mouse trophoblast cells by interferon-gamma
(W B Saunders Co Ltd, 2007-10-01) Hoshida, M. S.; Gorjao, R.; Lima, C.; Daher, S.; Curi, R.; Bevilacqua, E.; Universidade de São Paulo (USP); Butantan Inst; Universidade Federal de São Paulo (UNIFESP)
We have previously shown that interferon-gamma (IFN-gamma) activates phagocytosis and induces nitric oxide production in cultured mouse trophoblast cells. in the present study we examined the effect of this cytokine on ectoplacental cone and gene expression in trophoblast cells. Ectoplacental cones were obtained during the postimplantation period on gestational day 7.5 from CD-I mice and exposed to 100 U/mL IFN-gamma. Ectoplacental cone morphology, cell proliferation and death were also determined upon IFN-gamma treatment. Complementary DNA macroarray and semiquantitative RT-PCR were used to analyze gene expression. IFN-gamma treatment did not alter ectoplacental cone morphology, trophoblast cell proliferation or death. However, using gene array technology, we observed that IFN-gamma affected the developing trophoblast, altering the level of mRNA expression, which resulted in upregulation of 35 genes and downregulation of seven others. the upregulation of transcription factors and immune response-associated genes suggests that IFN-gamma is involved in processes beyond immunological homeostasis and plays an important role in placental development and function. (C) 2007 Elsevier B.V. All rights reserved.
Acesso aberto (Open Access)
Relationship between Anxiety and Interleukin 10 in Female Soccer Players with and Without Premenstrual Syndrome (PMS)
(Federacao Brasileira Soc Ginecologia & Obstetricia-Febrasgo, 2017) Foster, Roberta [UNIFESP]; Vaisberg, Mauro [UNIFESP]; de Araujo, Maita Poli [UNIFESP]; Martins, Marcia Aparecida [UNIFESP]; Capel, Tiago [UNIFESP]; Lacerda Bachi, Andre Luis; Katalin de Jarmy-Di Bella, Zsuzsanna Ilona [UNIFESP]
Objective To investigate the level of anxiety and its relationship with interleukin (IL)10 (anti inflammatory cytokine that modulates mood swings) in a group of female soccer players. Methods Fifty-two eumenorrheic soccer players were evaluated (age 19.8 +/- 4.7 years). The presence of premenstrual syndrome (PMS) and phases of the menstrual cycle were determined by a daily symptomreport (DSR) kept for 3 consecutivemonths. The concentration of cytokine IL-10 was determined from urine samples collected at four moments: at the follicular and luteal phases of the menstrual cycle, and before (pre) and after (post) the simulated game, and it was quantified by flow cytometry (Luminex xMAP - EMDMillipore, Billerica, MA, USA). The level of anxietywas determined through the BAI anxiety questionnaire answered by all athletes at the same time of the urine collection. The Student t-test, analysis of variance (ANOVA) and Pearson correlation with significance level at 5% were used for data analysis. Results We showed that the prevalence of PMS among female soccer players is similar to that reported in the literature. In addition, we showed that the group withPMS has a higher level of anxiety compared with group without PMS (p = 0.002). Interleukin-10 analysis in players without PMS revealed that there was a significant decrease in the level of this cytokine before the game during the luteal phase when compared with the follicular phase (p < 0.05). The correlation analysis between IL-10 and anxiety showed a negative correlation post-game in the luteal phase in the group without PMS (p = 0.02; r = -0.50) and a positive correlation post-game in the luteal phase in PMS group (p = 0.04; r = 0.36). Conclusion Our results suggest that IL-10 may contribute to reduce anxiety in the group without PMS. This could be attributed to the fact that no IL-10 variation was observed in the group with PMS, which presented higher anxiety symptoms when compared with the group without PMS.
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Serum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients
(Wiley-Blackwell, 2012-04-01) Gabbay, Monica Andrade Lima [UNIFESP]; Sato, M. N.; Duarte, A. J. S.; Dib, Sergio Atala [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); São Paulo State Univ
Several studies correlated genetic background and pancreatic islet-cell autoantibody status (type and number) in type 1A diabetes mellitus (T1AD), but there are no data evaluating the relationship among these markers with serum cytokines, regulatory T cells and beta cell function. This characterization has a potential importance with regard to T1AD patients' stratification and follow-up in therapeutic prevention. in this study we showed that peripheral sera cytokines [interleukin (IL)-12, IL-6, II-1 beta, tumour necrosis factor (TNF)-a, IL-10] and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in newly diagnosed T1AD patients when compared to healthy controls (P < 0.001). Among T1AD, we found a positive correlation between CXCL10 and CCL-2 (r = 0.80; P = 0.000), IL-8 and TNF-alpha (r = 0.60; P = 0.000); IL-8 and IL-12 (r = 0.57; P = 0.001) and TNF-alpha and IL-12 (r = 0.93; P = 0.000). Glutamic acid decarboxylase-65 (GAD-65) autoantibodies (GADA) were associated negatively with CXCL10 (r = -0.45; P = 0.011) and CCL2 (r = -0.65; P = 0.000), while IA-2A showed a negative correlation with IL-10 (r = -0.38; P = 0.027). Human leucocyte antigen (HLA) DR3, DR4 or DR3/DR4 and PTPN22 polymorphism did not show any association with pancreatic islet cell antibodies or cytokines studied. in summary, our results revealed that T1AD have a proinflammatory cytokine profile compared to healthy controls and that IA-2A sera titres seem to be associated with a more inflammatory peripheral cytokine/chemokine profile than GADA. A confirmation of these data in the pre-T1AD phase could help to explain the mechanistic of the well-known role of IA-2A as a more specific marker of beta-cell damage than GADA during the natural history of T1AD.
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TNF-alpha polymorphisms are associated with obsessive-compulsive disorder
(Elsevier B.V., 2008-09-12) Hounie, Ana Gabriela; Cappi, Carolina; Cordeiro, Quirino; Sampaio, Aline Santos; Moraes, Ivanil; Rosario, Maria Conceicao do [UNIFESP]; Palacios, Selma A.; Goldberg, Anna Carla; Vallada, Homero Pinto; Machado-Lima, Ariane; Nakano, Eduardo; Kalil, Jorge; Pauls, David; Pereira, Carlos Alberto B.; Guilherme, Luiza; Miguel, Euripedes Constantino; Universidade de São Paulo (USP); Harvard Univ; Universidade Federal de São Paulo (UNIFESP)
Introduction: Several lines of evidence support an immunologic involvement in obsessive-compulsive disorder (OCD): the increased prevalence of OCD in patients with rheumatic fever (RF), and the aggregation of obsessive-compulsive spectrum disorders among relatives of RF probands. Tumor necrosis factor alpha is a proinflammatory cytokine involved in RF and other autoimmune diseases. Polymorphisms in the promoter region of the TNFA gene have been associated with RE Given the association between OCD and RF, the goal of the present study was to investigate a possible association between polymorphisms within the promoter region of TNFA and OCD. Materials and methods: Two polymorphisms were investigated: -308 G/A and -238 G/A. the allelic and genotypic frequencies of these polymorphisms were examined in 111 patients who fulfilled DSM-IV criteria for OCD and compared with the frequencies in 250 controls. Results: Significant associations were observed between both polymorphisms and OCD. for -238 G/A, an association between the A allele and OCD was observed (X-2 = 12.05, p = 0.0005). A significant association was also observed between the A allele of the -308 G/A polymorphism and OCD (X-2 = 7.09, p = 0.007). Finally, a haplotype consisting of genotypes of these two markers was also examined. Significant association was observed for the A-A haplotype (p = 0.0099 after correcting for multiple testing). Discussion: There is association between the -308 G/A and -238 G/A TNFA polymorphisms and OCD in our Brazilian sample. However, these results need to be replicated in larger samples collected from different populations. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

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