Avaliação de IFN-γ e IL-10 em cães naturalmente infectados com Leishmania (Leishmania) chagasi com e sem manifestações clínicas / Evaluation of INF-γ and IL-10 in dogs naturally infected by Leishmania (Leishmania) chagasi with and without clinic events

As leishmanioses têm como agentes etiológicos parasitas intracelulares obrigatórios pertencentes ao gênero Leishmania capazes de infectar diferentes espécies de mamíferos e nestes se reproduzirem dentro do sistema fagocítico mononuclear. Os cães domésticos são os principais responsáveis pela manutenção da cadeia epidemiológica da doença, podendo apresentar uma grande variedade de perfis clínicos, desde aparentemente sadios a severamente acometidos. Avaliou-se a expressão das citocinas de cães naturalmente infectados com Leishmania (Leishmania) chagasi. Foram coletadas 50 amostras, sendo 20 de animais positivos e sintomáticos para Leishmaniose Visceral Canina (LVC), 20 de animais positivos e assintomáticos e 10 de animais sabidamente negativos para a LVC. As amostras foram analisadas pelo teste imunocromatográfico rápido Dual Path Platform (DPP/Biomanguinhos®) e pelo ELISA (EIE/Biomanguinhos®) indireto para detecção de anticorpos anti-Leishmania. Após as confirmações dos testes, foi realizado o ELISA de captura (R & D Systems) para quantificação das citocinas IL-10 e IFN-γ. Houve diferença estatística entre os grupos observando um aumento nos níveis de IFN-γ nos animais assintomáticos e um aumento de IL-10 nos sintomáticos.(AU)

Leishmaniasis has as obligatory intracellular parasitic etiological agents belonging to the genus Leishmania capable of infecting different species of mammals and reproducing them within the mononuclear phagocytic system. Domestic dogs are the main responsible for maintaining the epidemiological chain of the disease, presenting a wide variety of clinical profiles, from apparently healthy to severely affected. The expression of the cytokines from dogs naturally infected with Leishmania (Leishmania) chagasi was evaluated. Blood samples were collected from 50 animals, 20 from positive and symptomatic dogs for Leishmaniasis Canine (CVL), 20 from positive asymptomatic animals and 10 negative. Samples were analyzed by immunochromatographic test Dual Path Platform (DPP/Biomanguinhos®) and by indirect ELISA (EIE/Biomanguinhos®) for detection of anti-Leishmania antibodies. There was statistical difference between the groups observing an increase in IFN-γ levels in asymptomatic animals and an IL-10 increase in symptomatic.(AU)

NLRP3 inflammasome signaling as an early molecular response is negatively controlled by miR-186 in CFA-induced prosopalgia mice

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most frequently studied in the central nervous system and has been linked to neuropathic pain. In this study, a post-translational mechanism of microRNA (miR)-186 via regulating the expression of NLRP3 in the complete Freund's adjuvant (CFA)-treated mice was investigated. The injection of CFA was used to induce trigeminal neuropathic pain in mice. miRs microarray chip assay was performed in trigeminal ganglions (TGs). CFA treatment significantly increased the mRNA expression of NLRP3, interleukin (IL)-1β, and IL-18 in TGs compared to the control group. Moreover, 26 miRs were differentially expressed in TGs from trigeminal neuropathic pain mice, and the expression of miR-186 showed the lowest level of all the miRs. Further examination revealed that NLRP3 was a candidate target gene of miR-186. We delivered miR-186 mimics to CFA-treated mice. The head withdrawal thresholds of the CFA-treated mice were significantly increased by miR-186 mimics injection compared with CFA single treatment. The mRNA and protein expression of NLRP3, IL-1β, and IL-18 in TGs from trigeminal neuropathic pain mice were significantly inhibited by miR-186 mimics treatment compared to the CFA group. miR-186 was able to suppress the neuropathic pain via regulating the NLRP3 inflammasome signaling.

Caspase-1 Level in Synovial Fluid Is High in Patients with Spondyloarthropathy but Not in Patients with Gout

Activation of caspase-1 by NALP3 inflammasomes has been shown to be important in initiating acute gouty arthritis. The objectives of this study were to measure the levels of caspase-1 in synovial fluid in gout and various arthritides, and to elucidate the clinical significance of caspase-1 levels in synovial fluid. Caspase-1, IL-1beta, IL-18, and uric acid were measured in synovial fluid from 112 patients with gout and other arthritides, such as rheumatoid arthritis, osteoarthritis, and spondyloarthropathy. Caspase-1 in synovial fluid from patients with crystal-induced arthritis, inflammatory arthritis, osteoarthritis, and spondyloarthropathy was 35.9 +/- 86.7, 49.7 +/- 107.7, 2.1 +/- 7.0, and 152.6 +/- 155.7 pg/mL, respectively. The mean level and the frequency of high levels (> or =125 pg/mL) of caspase-1 in spondyloarthropathy were significantly higher than those in the other arthritides including gout. Caspase-1 was detectible in the synovial fluid of patients with the various arthritides. Contrary to our hypothesis, the caspase-1 level in the synovial fluid of patients with gout was not higher than in that of other arthritides. High levels of caspase-1 may be helpful in differentiating spondyloarthropathy from other arthritides.

role of interleukin-18 promoter polymorphisms [-607 C/A and 137 G/C ] in determining HCV clearance or persistence

Two interleukin [IL-18] Polymorphisms [- 607 C/A and -137 G/C] and their haplotypes are known to affect the IL-18 expression. A number of SNPs [single nucleotide polymorphisms] that influence IL- 18 production are found in the gene promoter region. The study will determine HCV clearance or persistence as a result of IL-18 promoter polymorphisms [-607 C/A and 137 G/C] in chronic hepatitis C virus infected patients during interferon and ribavirin treatment. Eighty patients with chronic hepatitis C virus infection, their age ranges between [23-57] years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during interferon and ribavirin therapy and fifteen healthy individuals were included to serve as controls. All the patients and controls were subjected to the following history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation, CBCs and serological assay and specific sequence primer polymerase chain reaction [PCR] IL-18-137, 607 SNP. There was no significant difference in the frequencies of -137 allelic distribution in CHCV infection patients and healthy controls. The -607 AA allele was higher among controls than in patients with CHCV infection. The -607 CC allele was higher among the CHCV patients than in the healthy controls. 87.5% of the studied CHCV patients had response to IFN therapy, the majority of cases had A1F1 biopsy results. IL-18 promoter polymorphism at -607 position with AA allele is a potential protective marker, as it is higher among healthy controls than the CHCV patients. That IL-18 could be considered as a target for therapeutics

Cytokine production in NK and NKT cells from Mycobacterium tuberculosis infected patients.

Tuberculosis, a major health problem in developing countries, has re-emerged in recent years in many countries. While it is accepted that various lymphocyte subsets are important responses to mycobacterial infection, the roles of NK and NKT cells in producing cytokines are still unclear. Thus we have evaluated, in Mycobacterium tuberculosis infection, the frequency of cytokine producing cells by flow cytometry. Of 30 individuals examined, 17 had clinical evidence of pulmonary tuberculosis while the rest showed no evidence of infection. Patients had a significantly higher number of IFN-gamma and IL-4-producing T cells compared to control subjects, but the ratio of IFN-gamma to IL-4-producing T cells was similar in both groups. There were no differences between cytokine profiles of NK cells in patients and control subjects. A significant increase in the number of NKT cells was observed in patients. A striking finding was the higher frequency of IL-4-producing NKT cells compared to IFN-gamma-producing cells. Moreover, individual NKT cell produced both IFN-gamma and IL-4. The preferential type of Thl or Th2 cells is due to mycobacterial strain, type of antigen presenting cells and stage of disease, all of which can lead to different patterns of cytokine production by variety of lymphocyte subsets.