T helper type cytokines in sepsis: time-shared variance and correlation with organ dysfunction and hospital mortality

ABSTRACT Objective: We evaluated the kinetics of cytokines belonging to the T helper1 (Th1), Th2, and Th17 profiles in septic patients, and their correlations with organ dysfunction and hospital mortality. Methods: This was a prospective observational study in a cohort of septic patients admitted to the intensive care units (ICU) of three Brazilian general hospitals. A total of 104 septic patients and 53 health volunteers (controls) were included. Plasma samples were collected within the first 48 h of organ dysfunction or septic shock (0D), after seven (D7) and 14 days (D14) of follow-up. The following cytokines were measured by flow cytometry: Interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-10, IL-12/23p40, IL-17, IL-21, tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF). Results: IL-6, IL-8, G-CSF and IL-10 concentrations were higher in septic patients than in controls (p < 0.001), while IL-12/23p40 presented higher levels in the controls (p = 0.003). IL-6, IL-8 and IL-17 correlated with Sequential [Sepsis-related] Organ Failure Assessment (SOFA) D0, D1 and D3 (except for IL-6 at D0). IL-8 was associated with renal and cardiovascular dysfunction. In a mixed model analysis, IL-10 estimated means were lower in survivors than in deceased (p = 0.014), while IL-21 had an estimated mean of 195.8 pg/mL for survivors and 98.5 for deceased (p = 0.03). Cytokines were grouped in four factors according to their kinetics over the three dosages (D0, D7, D14). Group 1 encompassed IL-6, IL-8, IL-10, IL-1β, and G-CSF while Group 3 encompassed IL-17 and IL-12/23p40. Both correlated with SOFA (D0) (p = 0.039 and p = 0.003, respectively). IL-21 (Group 4) was higher in those who survived. IL-2, TNF-α and GM-CSF (Group 2) showed no correlation with outcomes. Conclusion: Inflammatory and anti-inflammatory cytokines shared co-variance in septic patients and were related to organ dysfunctions and hospital mortality.

Intestinal parasites infection: protective effect in rheumatoid arthritis? / Parasitoses intestinais: efeito protetor na artrite reumatoide?

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, with a progressive course, characterized by chronic synovitis that may evolve with deformities and functional disability, and whose early treatment minimizes joint damage. Its etiopathogenesis is not fully elucidated but comprises immunologic responses mediated by T helper cells (Th1). An apparent minor severity of RA in patients from regions with lower income could be associated with a higher prevalence of gut parasites, especially helminths. Strictly, a shift in the immune response toward the predominance of T helper cells (Th2), due to the chronic exposure to helminths, could modulate negatively the inflammation in RA patients, resulting in lower severity/joint injury. The interaction between the immunological responses of parasitic helminths in rheumatoid arthritis patients is the purpose of this paper.

Resumo A artrite reumatoide (AR) é uma doença inflamatória autoimune, sistêmica, de curso progressivo, caracterizada por exuberante sinovite crônica, que pode gerar deformidades e incapacidade funcional, cujo tratamento precoce minimiza o dano às juntas. Sua etiopatogenia ainda não está completamente elucidada, mas compreende respostas imunológicas com a participação de células T auxiliares (Th1). Uma aparente menor gravidade da AR em pacientes de regiões com menor renda poderia estar associada a maior prevalência de parasitoses intestinais, especialmente as helmintíases. A rigor, um desvio na resposta imune para o predomínio de células T auxiliares (Th2), decorrente da exposição crônica a helmintos, modularia negativamente a inflamação em doentes com AR, e levaria a menor gravidade e dano articular. A revisão de aspectos da influência da reposta imunológica nas parasitoses intestinais, especialmente as helmintíases, em pacientes com artrite reumatoide é o objetivo desse trabalho.

Citocinas de resposta Th1 e Th2 e diabetes mellitus tipo 1 / Th1 and Th2 response cytokins in type 1 diabetes mellitus

O diabetes mellitus tipo 1 (DM1) é uma doença autoimune crônica, onde as células T autorreativas destroem as células beta pancreáticas levando à dependência de insulina exógena. Para o desenvolvimento do DM1 são necessárias numerosas interações entre as células do sistema imunológico, principalmente mediadas por citocinas de resposta T helper 1 (Th1) e T helper 2 (Th2). O presente estudo teve como objetivo analisar a relação das citocinas de resposta Th1 e Th2 no desenvolvimento do DM1 por meio de uma revisão de literatura, avaliando artigos científicos eletrônicos publicados entre os anos de 2001 e 2016, além de livros de imunologia aplicados à clínica. Diversos estudos na literatura demonstram que o perfil de secreção de citocinas durante o desenvolvimento do DM1 é de padrão Th1 onde temos como principais constituintes a IL-2 e o IFN-y. Já as citocinas de resposta Th2, compostas basicamente pela IL-4, IL-6 e IL-10, são responsáveis por bloquear a evolução do DM1. Através desses dados conclui-se que o entendimento dos aspectos imunológicos constitui a base para detecção e prevenção do DM1, sendo a disponibilidade de citocinas clonadas e purificadas uma nova perspectiva para terapias clínicas específicas para modular a resposta imune

Type 1 diabetes mellitus (DM1) is a chronic autoimmune disease, where as autoreactive T cells destroy as pancreatic beta cells leading to exogenous insulin dependence. For the development of DM1, interactions between immune system cells, mainly mediated by cytokines of T helper 1 (Th1) and T helper 2 (Th2) are required. The present study aimed to analyze the relationship of Th1 and Th2 response cytokines in the development of DM1, through a review of the literature, evaluating electronic scientific articles published between 2001 and 2016, as well as immunology books applied to the clinic. Several studies in the literature demonstrate that the cytokine secretion profile during the development of DM1 is of the Th1 pattern where we have as main constituent of IL-2 and IFN-γ. As Th2 response cytokines, composed mainly of IL-4, IL-6 and IL-10, they are responsible for blocking the progression of DM1. Through conclusive data, it is a point of view for the prevention of DM1. With the availability of cloned and purified cytokines a new perspective for specific clinical therapies to modulate the immune response

Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases

Chronic Schistosoma mansoni infection leads to a type 2-immune response with increased production of interleukin (IL-10). Evidence indicates chronic exposure to S. mansoni down regulates the type 1 immune response and prevents the onset of Th1-mediated diseases such as multiple sclerosis, diabetes mellitus and Cronh's disease. Furthermore, our own studies have revealed that chronic exposure to S. mansoni also down regulates atopic disease, Th2-mediated diseases. Our studies show an inverse association between the skin prick test reactivity and infection with S. mansoni and show the severity of asthma is reduced in subjects living in an endemic area of S. mansoni. Moreover, we hypothesize the mechanisms involved in the modulation of inflammatory response in atopic individuals, is likely dependent on IL-10 production, an anti-inflammatory cytokine elevated during helminth infections. Patients with asthma and helminth infections produced less IL-5 than patients with asthma without helminth infections, and this down regulation could, in part, be mediated by IL-10. In conclusion, helminthic infections, through induction of regulatory mechanisms, such as IL-10 production, are able to modulate the inflammatory immune response involved in the pathology of auto-immune and allergic disease.

Experimental models of Schistosoma mansoni infection

Experimental models of Schistosoma mansoni infections in mammals have contributed greatly to our understanding of the pathology and pathogenesis of infection. We consider here hepatic and extrahepatic disease in models of acute and chronic infection. Experimental schistosome infections have also contributed more broadly to our understanding of granulomatous inflammation and our understanding of Th1 versus Th2 related inflammation and particularly to Th2-mediated fibrosis of the liver