Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (H2O2) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA). We also assessed whether TRPA1 expression correlates with joint pain and disability, in addition to the immune changes in RA. TRPA1 expression on peripheral blood leukocytes correlated with pain severity and disability. TRPA1 levels on these cells were associated with the numbers of polymorphonuclear and the activation of CD14+ cells. No correlations were found between the lymphocyte population and TRPA1 expression, pain or disability. Patients recently diagnosed with RA expressed increased levels of TRPA1 on their leukocytes whilst treatment with either LFN or ADA down-regulated this receptor probably by reducing the numbers of polymorphonuclears and the activation of CD14+ cells. We suggest that the activation levels of CD14+ cells, the numbers of PMNs in the peripheral blood and the expression of TRPA1 on peripheral blood leukocytes correlate with RA progression, affecting joint pain sensitivity and loss of function.

Rheumatoid arthritis (RA) is characterized by inflammation of one or more joints, and affects ~1% of the adult population worldwide. Sulforaphane (SFN) is a natural compound that has been suggested as an antioxidant. Here, SFN’s effects were evaluated in a murine mono-arthritis model. Mono-arthritis was induced in mice by a single intra-articular injection of Complete Freund’s Adjuvant (CFA-10 µg/joint, in 10 µL) into the ipsilateral joint. The contralateral joint received an equal volume of PBS. On the 4th day post-joint inflammation induction, animals received either SFN (10 mg/kg) or vehicle (3% DMSO in saline), intraperitoneally (i.p.), twice a day for 3 days. Joint swelling and secondary mechanical allodynia and hyperalgesia were evaluated over 7 days post-CFA. After this period, animals were culled and their blood and synovial fluid samples were collected for analysis of cell populations, cytokine release and thioredoxin reductase (TrxR) activity. Knee joint samples were also collected for histology. SFN reduced joint swelling and damage whilst increasing the recruitment of Ly6C+ and Ly6G+ cells to CFA-injected joints. SFN-treated animals presented down-regulation of CD11b and CD62L on synovial fluid Ly6G+ cells. Synovial fluid samples obtained from CFA-injected joints and plasma samples of SFN-treated mice presented higher levels of IL-6 and increased activity of TrxR, in comparison with controls. These results indicate that SFN reduces knee joint damage by modulating cell activation/migration to the joints, cytokine production and increasing the activity of TrxR, and therefore, may represent an alternative treatment to joint inflammation.

Rheumatoid arthritis is a chronic disease of the joints, which causes joint pain and disability. Anaemia is a frequent extra-articular manifestation in rheumatoid arthritis, affecting 30-70% of the patients; presenting a negative impact on patient´s quality of life. Some of the drugs used in rheumatoid arthritis treatment improve anaemia; but little is known on the beneficial effects of the anti-rheumatic leflunomide or the anti-TNFα adalimumab, in this parameter. We investigated the incidence of anaemia in rheumatoid arthritis patients treated or not with leflunomide or adalimumab. We also assessed whether anaemia correlates with disease activity. Anaemia was present in patients who had just been diagnosed with rheumatoid arthritis and had never taken disease modifying agents or biologicals (non-specific therapy group), but not in those taking either leflunomide or adalimumab. The erythrocyte sedimentation rate was increased in patients with non-specific therapy in comparison with those taking either leflunomide or adalimumab. Anaemia correlated with increased erythrocyte sedimentation rate. We suggest that leflunomide and adalimumab may be useful in treating anaemia in patients with rheumatoid arthritis.

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A malária é uma doença infecciosa aguda causada por protozoários do gênero Plasmodium e transmitida ao homem pela picada da fêmea do mosquito Anopheles. O P. vivax é uma das 5 espécies que infectam os seres humanos, sendo uma das mais prevalentes na região Amazônica. Este trabalho tem como objetivo analisar marcadores de ativação do sistema imune durante a infecção pelo Plasmodium vivax em infectados residentes na cidade de Cruzeiro do Sul (AC), uma área de transmissão ativa de malária, de modo a se verificar as mudanças que tal infecção provoca no sistema imune. O sangue periférico dos pacientes e controles foi coletado para realização do hemograma e da fenotipagem por citometria de fluxo. Em todos os grupos analisados foi realizado teste de normalidade Shapiro-Wilk nas variáveis numéricas. Foi encontrada uma leucopenia periférica significativa no grupo infectado se comprada ao grupo controle. Quanto a frequência de monócitos e linfócitos totais, não foi encontrada diferença significativa, porém, estudos demonstram que há uma grande ativação de subpopulações de linfócitos. A infecção induziu o aumento de marcadores de ativação (CD69 e HLA-DR) em células T dos indivíduos acometidos pelo Plasmodium vivax. Em conjunto, esses dados sugerem que a infecção pelo P. vivax promove ativação de linfócitos T, uma vez que altera significantemente a expressão de marcadores de ativação. Estes resultados apontam para a necessidade gerar informações acerca dos mecanismos imunológicos na malária pelo P. vivax que poderão subsidiar o desenvolvimento de futuras pesquisas sobre essa temática e consequentemente novas medidas de intervenção. PALAVRAS-CHAVE: Plasmodium vivax, Imunologia, marcadores de ativação.