Quality of life and strength, but not cytokines, are associated with DAS-28 in active and inactive rheumatoid arthritis / Qualidade de vida e força, porém não as citocinas, estão associadas ao DAS-28 em pacientes com artrite reumatoide na fase ativa e inativa

Objective: Evaluate and correlate data between relevant cytokines, disease progression, and handgrip and quality of life among RA patients at different stages of disease progression. Method: Thirty-three RA patients were recruited for analysis, using comparisons and correlations, between levels of circulating cytokines (IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17, IL-1ß, and TNF receptors I and II), activity of the disease (evaluated using the DAS-28), handgrip (Hydraulic dynamometer), and quality of life (SF-36). Result: RA patients in different disease stages showed increases of IL-6 and IL-10 compared control group. Positive correlation between IL-6 with TNF-α, and IL-4 with IL-10 was found. Handgrip strength and quality of life were not related to cytokine levels. However, remission patients had better strength and quality of life indices compared to the active patients. In addition, handgrip of the non-dominant side, physical functions, role limitations physical health, pain, energy/fatigue and social functions have a negative correlation with the DAS28-PCR. Conclusion: High levels of IL-6 and IL-10 were observed in the chronic RA patients, but the values did not show correlation with disease activity, handgrip strength and quality of life. Disease activity show correlation with handgrip strength and quality of life. Furthermore, remission patients had better strength and quality of life indices compared to the active patients.

Objetivo: Avaliar e correlacionar dados entre citocinas relevantes, progressão da doença, preensão manual e qualidade de vida entre pacientes com AR em diferentes estágios de progressão da doença. Método: Trinta e três pacientes com AR foram recrutados para análise, por meio de comparações e correlações, entre níveis de citocinas circulantes (IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17, IL-1ß e receptores de TNF-I e -II), atividade da doença (avaliada pelo DAS-28), preensão manual (dinamômetro hidráulico) e qualidade de vida (SF-36). Resultado: Pacientes com doença ativa e inativa apresentaram aumento de IL-6 e IL-10 comparados ao grupo controle. Foi encontrada correlação positiva entre IL-6 com TNF-α e IL-4 com IL-10. A força de preensão e a qualidade de vida não relacionaram aos níveis de citocinas. Entretanto, pacientes em remissão apresentaram melhores índices de força e qualidade de vida comparados aos pacientes com doença ativa. Além disso, preensão manual do lado não dominante, e quesitos dos SF-36, apresentam correlação negativa com o DAS28-PCR. Conclusão: Foram observados níveis elevados de IL-6 e IL-10 nos pacientes com AR crônica, mas os valores não mostraram correlação com DAS-28, força de preensão manual e SF-36. A atividade da doença apresenta correlação com força de preensão manual e qualidade de vida. Além disso, os pacientes em remissão apresentaram melhores índices de força e qualidade de vida em comparação aos pacientes ativos.

Metallic nanoparticles and treatment of cutaneous leishmaniasis: A systematic review.

BACKGROUND: Cutaneous leishmaniasis (LC) is an infectious vector-borne disease caused by parasites belonging to the genus Leishmania. Metallic nanoparticles (MNPs) have been investigated as alternatives for the treatment of LC owing to their small size and high surface area. Here, we aimed to evaluate the effect of MNPs in the treatment of LC through experimental, in vitro and in vivo investigations. METHODS: The databases used were MEDLINE/ PubMed, Scopus, Web of Science, Embase, and Science Direct. Manual searches of the reference lists of the included studies and grey literature were also performed. English language and experimental in vitro and in vivo studies using different Leishmania species, both related to MNP treatment, were included. This study was registered in PROSPERO (CRD42021248245). RESULTS: A total of 93 articles were included. Silver nanoparticles are the most studied MNPs, and L. tropica is the most studied species. Among the mechanisms of action of MNPs in vitro, we highlight the production of reactive oxygen species, direct contact of MNPs with the biomolecules of the parasite, and release of metal ions. CONCLUSION: MNPs may be considered a promising alternative for the treatment of LC, but further studies are needed to define their efficacy and safety.

Macrophage Migration Inhibitory Factor contributes to drive phenotypic and functional macrophages activation in response to Toxoplasma gondii infection.

Cytokines are small molecules secreted by numerous cells. Macrophage Migration Inhibitory Factor (MIF) is a cytokine initially described due to its function of inhibiting random macrophage migration. Currently, new functions have been described for MIF, such as stimulating inflammatory functions in response to infections by microorganisms including, Toxoplasma gondii. However, the primordial MIF function related to macrophages has been little addressed. The main purpose of the study was to recapitulate MIF function on macrophages in response to T. gondii infection. To achieve this goal, peritoneal macrophages were collected from C57BL/6WT and Mif1-/- mice after recruitment with thioglycolate. Macrophages were cultured, treated with 4-Iodo-6-phenylpyrimidine (4-IPP), and infected or not by T. gondii for 24 h. Following this, the culture supernatant was collected for cytokine, urea and nitrite analysis. In addition, macrophages were evaluated for phagocytic activity and T. gondii proliferation rates. Results demonstrated that T. gondii infection triggered an increase in MIF production in the WT group as well as an increase in the secretion of IL-10, TNF, IFN-γ, IL-6 and IL-17 in the WT and Mif1-/- macrophages. Regarding the comparison between groups, it was detected that Mif1-/- macrophages secreted more IL-10 compared to WT. On the other hand, the WT macrophages produced greater amounts of TNF, IFN-γ, IL-6 and IL-17. Urea production was more pronounced in Mif1-/- macrophages while nitrite production was higher in WT macrophages. T. gondii showed a greater ability to proliferate in Mif1-/- macrophages and these cells also presented enhanced phagocytic activity. In conclusion, T. gondii infection induces macrophage activation inciting cytokine production. In presence of MIF, T. gondii infected macrophages produce pro-inflammatory cytokines compatible with the M1 activation profile. MIF absence caused a dramatic reduction in pro-inflammatory cytokines that are balanced by increased levels of urea and anti-inflammatory cytokines. These macrophages presented increased phagocytic capacity and shared features activation with the M2 profile.

Development of Ag-ZnO/AgO Nanocomposites Effectives for Leishmania braziliensis Treatment.

Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania. Leishmania braziliensis (L.b) is one of the most clinically relevant pathogens that affects the skin and mucosa, causing single or multiple disfiguring and life-threatening injuries. Even so, the few treatment options for patients have significant toxicity, high dropout rates, high cost, and the emergence of resistant strains, which implies the need for studies to promote new and better treatments to combat the disease. Zinc oxide nanocrystals are microbicidal and immunomodulatory agents. Here, we develop new Ag-ZnO/xAgO nanocomposites (NCPs) with three different percentages of silver oxide (AgO) nanocrystals (x = 49%, 65%, and 68%) that could act as an option for tegumentary leishmaniasis treatment. Our findings showed that 65% and 68% of AgO inhibit the extra and intracellular replication of L.b. and present a high selectivity index. Ag-ZnO/65%AgO NCPs modulate activation, expression of surface receptors, and cytokine production by human peripheral blood mononuclear cells toward a proinflammatory phenotype. These results point to new Ag-ZnO/AgO nanocomposites as a promising option for L. braziliensis treatment.

Association of Proinflammatory Cytokine Levels with Stroke Severity, Infarct Size, and Muscle Strength in the Acute Phase of Stroke.

OBJECTIVE: Patterns of cytokine levels and their association with stroke severity, infarct size, and muscle strength are obscure. We aimed to analyze the immune mediators linked to T helper (Th)1, Th2, Th17, and regulatory T cell patterns and their association with stroke severity, infarct size, and muscle strength. MATERIALS AND METHODS: We included patients with acute stroke (n = 15) and healthy non-disabled individuals (n = 20) aged > 18 years. The dependent variables were stroke severity according to the National Institute of Health Stroke Scale (NIHSS), infarct size on computed tomography, handgrip strength by dynamometry, and global muscle strength according to the Medical Research Council (MRC) scale. The independent variables were the circulating cytokine levels. The cytokine levels were compared between the groups, and correlations between the clinical data were verified. RESULTS: The stroke group had higher interleukin (IL)-6 (p < 0.0001) and IL-10 (p < 0.0001) levels, but lower tumor necrosis factor (TNF)-α (p = 0.036) levels than the control group. IL-10 and soluble tumor necrosis factor receptor (sTNF-RII) levels were correlated with each other (r = 0.533; p = 0.042) and infarct size (r = 0.653; p = 0.033 and r = 0.689; p = 0.018, respectively). MRC scores were positively and negatively correlated with handgrip strength of the affected side (r = 0.78; p = 0.001) and NIHSS scores (r = -0.87; p < 0.0001), respectively. CONCLUSIONS: Plasma levels of some cytokines were associated with changes in the acute phase of stroke, and IL-10 and sTNF-RII levels are potential biomarkers of infarct size.