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1.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200882

RESUMO

The occurrence of microbial challenges in commercial poultry farming causes significant economic losses. Antibiotics have been used to control diseases involving bacterial infection in poultry. As the incidence of antibiotic resistance turns out to be a serious problem, there is increased pressure on producers to reduce antibiotic use. With the reduced availability of antibiotics, poultry producers are looking for feed additives to stimulate the immune system of the chicken to resist microbial infection. Some ß-glucans have been shown to improve gut health, to increase the flow of new immunocytes, increase macrophage function, stimulate phagocytosis, affect intestinal morphology, enhance goblet cell number and mucin-2 production, induce the increased expression of intestinal tight-junctions, and function as effective anti-inflammatory immunomodulators in poultry. As a result, ß-glucans may provide a new tool for producers trying to reduce or eliminate the use of antibiotics in fowl diets. The specific activity of each ß-glucan subtype still needs to be investigated. Upon knowledge, optimal ß-glucan mixtures may be implemented in order to obtain optimal growth performance, exert anti-inflammatory and immunomodulatory activity, and optimized intestinal morphology and histology responses in poultry. This review provides an extensive overview of the current use of ß glucans as additives and putative use as antibiotic alternative in poultry.


Assuntos
Antibacterianos/farmacologia , beta-Glucanas/farmacologia , Ração Animal , Animais , Anti-Inflamatórios/farmacologia , Humanos , Fatores Imunológicos/farmacologia , Carne , Aves Domésticas
2.
Int Immunopharmacol ; 96: 107761, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34162139

RESUMO

Since the discovery of lymphocytes with immunosuppressive activity, increasing interest has arisen in their possible influence on the immune response induced by vaccines. Regulatory T cells (Tregs) are essential for maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. However, they also limit beneficial immune responses by suppressing anti-infectious and anti-tumor immunity. Mounting evidence suggests that Tregs are involved, at least in part, in the low effectiveness of immunization against various diseases where it has been difficult to obtain protective vaccines. Interestingly, increased activity of Tregs is associated with aging, suggesting a key role for these cells in the lower vaccine effectiveness observed in older people. In this review, we analyze the impact of Tregs on vaccination, with a focus on older adults. Finally, we address an overview of current strategies for Tregs modulation with potential application to improve the effectiveness of future vaccines targeting older populations.


Assuntos
Doenças Autoimunes/terapia , Doença Crônica/terapia , Inflamação/terapia , Linfócitos T Reguladores/fisiologia , Vacinas/imunologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Doenças Autoimunes/imunologia , Humanos , Fatores Imunológicos/farmacologia , Imunomodulação/fisiologia , Imunossupressores/farmacologia , Inflamação/imunologia , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Vacinação
3.
Int Immunopharmacol ; 96: 107797, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34162159

RESUMO

Specific antibodies against SARS-CoV-2 structural protein have a wide range of effects in the diagnose, prevention and treatment of the COVID-19 epidemic. Among them, egg yolk immunoglobulin Y (IgY), which has high safety, high yield, and without inducing antibody-dependent enhancement, is an important biological candidate. In this study, specific IgY against the conservative nucleocapsid protein (NP) of SARS-CoV-2 was obtained by immunizing hens. Through a series of optimized precipitation and ultrafiltration extraction schemes, its purity was increased to 98%. The hyperimmune IgY against NP (N-IgY) at a titer of 1:50,000 showed strong NP binding ability, which laid the foundation of N-IgY's application targeting NP. In an in vitro immunoregulatory study, N-IgY (1 mg/mL) modulated NP-induced immune response by alleviating type II interferon secretion stimulated by NP (20 µg/mL). In summary, N-IgY can be mass produced by achievable method, which endows it with potential value against the current COVID-19 pandemic.


Assuntos
Anticorpos/imunologia , Antivirais/imunologia , COVID-19/imunologia , Imunoglobulinas/imunologia , Fatores Imunológicos/imunologia , Interferon gama/metabolismo , SARS-CoV-2/imunologia , Animais , Anticorpos/farmacologia , Antivirais/farmacologia , COVID-19/terapia , Galinhas , Desenvolvimento de Medicamentos , Gema de Ovo/química , Gema de Ovo/metabolismo , Humanos , Imunidade , Imunoglobulinas/farmacologia , Fatores Imunológicos/farmacologia , Imunomodulação , Técnicas In Vitro , Proteínas do Nucleocapsídeo/imunologia , Proteínas do Nucleocapsídeo/metabolismo , SARS-CoV-2/metabolismo
4.
Eur Rev Med Pharmacol Sci ; 25(11): 4174-4184, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-1281023

RESUMO

Currently, the COVID-19 pandemic, caused by the novel SARS-CoV-2 coronavirus, represents the greatest global health threat. Most people infected by the virus present mild to moderate respiratory symptoms and recover with supportive treatments. However, certain susceptible hosts develop an acute respiratory distress syndrome (ARDS), associated with an inflammatory "cytokine storm", leading to lung damage. Despite the current availability of different COVID-19 vaccines, the new emerging SARS-CoV-2 genetic variants represent a major concern worldwide, due to their increased transmissibility and rapid spread. Indeed, it seems that some mutations or combinations of mutations might confer selective advantages to the virus, such as the ability to evade the host immune responses elicited by COVID-19 vaccines. Several therapeutic approaches have been investigated but, to date, a unique and fully effective therapeutic protocol has not yet been achieved. In addition, steroid-based therapies, aimed to reduce inflammation in patients with severe COVID-19 disease, may increase the risk of opportunistic infections, increasing the hospitalization time and mortality rate of these patients. Hence, there is an unmet need to develop more effective therapeutic options. Here, we discuss the potential use of natural immunomodulators such as Thymosin α1 (Tα1), all-trans retinoic acid (ATRA), and lactoferrin (LF), as adjunctive or preventive treatment of severe COVID-19 disease. These agents are considered to be multifunctional molecules because of their ability to enhance antiviral host immunity and restore the immune balance, depending on the host immune status. Furthermore, they are able to exert a broad-spectrum antimicrobial activity by means of direct interactions with cellular or molecular targets of pathogens or indirectly by increasing the host immune response. Thus, due to the aforementioned properties, these agents might have a great potential in a clinical setting, not only to counteract SARS-CoV-2 infection, but also to prevent opportunistic infections in critically ill COVID-19 patients.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/imunologia , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Humanos , Fatores Imunológicos/farmacologia , Lactoferrina/imunologia , Lactoferrina/farmacologia , Lactoferrina/uso terapêutico , Tretinoína/imunologia , Tretinoína/farmacologia , Tretinoína/uso terapêutico
5.
Int J Mol Sci ; 22(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: covidwho-1244040

RESUMO

The COVID-19 pandemic has established an unparalleled necessity to rapidly find effective treatments for the illness; unfortunately, no specific treatment has been found yet. As this is a new emerging chaotic situation, already existing drugs have been suggested to ameliorate the infection of SARS-CoV-2. The consumption of caffeine has been suggested primarily because it improves exercise performance, reduces fatigue, and increases wakefulness and awareness. Caffeine has been proven to be an effective anti-inflammatory and immunomodulator. In airway smooth muscle, it has bronchodilator effects mainly due to its activity as a phosphodiesterase inhibitor and adenosine receptor antagonist. In addition, a recent published document has suggested the potential antiviral activity of this drug using in silico molecular dynamics and molecular docking; in this regard, caffeine might block the viral entrance into host cells by inhibiting the formation of a receptor-binding domain and the angiotensin-converting enzyme complex and, additionally, might reduce viral replication by the inhibition of the activity of 3-chymotrypsin-like proteases. Here, we discuss how caffeine through certain mechanisms of action could be beneficial in SARS-CoV-2. Nevertheless, further studies are required for validation through in vitro and in vivo models.


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , COVID-19/dietoterapia , Cafeína/farmacologia , Reposicionamento de Medicamentos/métodos , Músculo Liso/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , COVID-19/metabolismo , COVID-19/fisiopatologia , Humanos , Fatores Imunológicos/farmacologia , Simulação de Dinâmica Molecular , Músculo Liso/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo
6.
Int Immunopharmacol ; 96: 107761, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-1253056

RESUMO

Since the discovery of lymphocytes with immunosuppressive activity, increasing interest has arisen in their possible influence on the immune response induced by vaccines. Regulatory T cells (Tregs) are essential for maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. However, they also limit beneficial immune responses by suppressing anti-infectious and anti-tumor immunity. Mounting evidence suggests that Tregs are involved, at least in part, in the low effectiveness of immunization against various diseases where it has been difficult to obtain protective vaccines. Interestingly, increased activity of Tregs is associated with aging, suggesting a key role for these cells in the lower vaccine effectiveness observed in older people. In this review, we analyze the impact of Tregs on vaccination, with a focus on older adults. Finally, we address an overview of current strategies for Tregs modulation with potential application to improve the effectiveness of future vaccines targeting older populations.


Assuntos
Doenças Autoimunes/terapia , Doença Crônica/terapia , Inflamação/terapia , Linfócitos T Reguladores/fisiologia , Vacinas/imunologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Doenças Autoimunes/imunologia , Humanos , Fatores Imunológicos/farmacologia , Imunomodulação/fisiologia , Imunossupressores/farmacologia , Inflamação/imunologia , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Vacinação
7.
Life Sci ; 280: 119700, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34111465

RESUMO

AIMS: This study evaluated the effect of euphol isolated from Euphorbia umbellata (Pax) Bruyns latex on the activation of complement pathways (classical (CP), alternative (AP) and lectin (LP)), neutrophil chemotaxis, cytotoxic activity, cell morphology and death in HRT-18 and 3T3 cells lines. MAIN METHODS: CP and AP were assessed using hemolytic assays and ELISA for LP; neutrophil chemotaxis was performed using Boyden's chamber; cytotoxicity was evaluated by neutral red methodology and characteristics of cell death were assessed by cell morphology with hematological staining. KEY FINDINGS: Although euphol increased CP activation (38% at a concentration of 976.1 µM), an inhibitory effect on AP, LP (31% and 32% reduction in the concentration of 976.1 µM) and neutrophil chemotaxis (inhibit 84% of neutrophil migration at a concentration 292.9 µM) was observed. In addiction euphol was able to induce significant cell death in a time-dependent manner, presenting an IC50 of 70.8 µM and 39.2 µM for HRT-18 and 3T3 cell lines respectively and it was also observed apoptotic characteristics as cellular rounding, chromatin condensation and blebs formation for both cell lines. SIGNIFICANCE: Euphol has a potential use for the treatment of complement-related inflammatory diseases due to its ability to downregulate inflammation. On the other hand, the controlled activation of CP can contribute to complement-dependent cytotoxicity in the context of monoclonal antibody-based cancer treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ativação do Complemento/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Lanosterol/análogos & derivados , Células 3T3 , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Euphorbia/química , Humanos , Lanosterol/farmacologia , Camundongos , Neoplasias/tratamento farmacológico
8.
Int Immunopharmacol ; 96: 107797, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-1300822

RESUMO

Specific antibodies against SARS-CoV-2 structural protein have a wide range of effects in the diagnose, prevention and treatment of the COVID-19 epidemic. Among them, egg yolk immunoglobulin Y (IgY), which has high safety, high yield, and without inducing antibody-dependent enhancement, is an important biological candidate. In this study, specific IgY against the conservative nucleocapsid protein (NP) of SARS-CoV-2 was obtained by immunizing hens. Through a series of optimized precipitation and ultrafiltration extraction schemes, its purity was increased to 98%. The hyperimmune IgY against NP (N-IgY) at a titer of 1:50,000 showed strong NP binding ability, which laid the foundation of N-IgY's application targeting NP. In an in vitro immunoregulatory study, N-IgY (1 mg/mL) modulated NP-induced immune response by alleviating type II interferon secretion stimulated by NP (20 µg/mL). In summary, N-IgY can be mass produced by achievable method, which endows it with potential value against the current COVID-19 pandemic.


Assuntos
Anticorpos/imunologia , Antivirais/imunologia , COVID-19/imunologia , Imunoglobulinas/imunologia , Fatores Imunológicos/imunologia , Interferon gama/metabolismo , SARS-CoV-2/imunologia , Animais , Anticorpos/farmacologia , Antivirais/farmacologia , COVID-19/terapia , Galinhas , Desenvolvimento de Medicamentos , Gema de Ovo/química , Gema de Ovo/metabolismo , Humanos , Imunidade , Imunoglobulinas/farmacologia , Fatores Imunológicos/farmacologia , Imunomodulação , Técnicas In Vitro , Proteínas do Nucleocapsídeo/imunologia , Proteínas do Nucleocapsídeo/metabolismo , SARS-CoV-2/metabolismo
9.
Int J Mol Sci ; 22(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067243

RESUMO

The COVID-19 pandemic has established an unparalleled necessity to rapidly find effective treatments for the illness; unfortunately, no specific treatment has been found yet. As this is a new emerging chaotic situation, already existing drugs have been suggested to ameliorate the infection of SARS-CoV-2. The consumption of caffeine has been suggested primarily because it improves exercise performance, reduces fatigue, and increases wakefulness and awareness. Caffeine has been proven to be an effective anti-inflammatory and immunomodulator. In airway smooth muscle, it has bronchodilator effects mainly due to its activity as a phosphodiesterase inhibitor and adenosine receptor antagonist. In addition, a recent published document has suggested the potential antiviral activity of this drug using in silico molecular dynamics and molecular docking; in this regard, caffeine might block the viral entrance into host cells by inhibiting the formation of a receptor-binding domain and the angiotensin-converting enzyme complex and, additionally, might reduce viral replication by the inhibition of the activity of 3-chymotrypsin-like proteases. Here, we discuss how caffeine through certain mechanisms of action could be beneficial in SARS-CoV-2. Nevertheless, further studies are required for validation through in vitro and in vivo models.


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , COVID-19/dietoterapia , Cafeína/farmacologia , Reposicionamento de Medicamentos/métodos , Músculo Liso/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , COVID-19/metabolismo , COVID-19/fisiopatologia , Humanos , Fatores Imunológicos/farmacologia , Simulação de Dinâmica Molecular , Músculo Liso/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo
10.
Eur Rev Med Pharmacol Sci ; 25(11): 4174-4184, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34156699

RESUMO

Currently, the COVID-19 pandemic, caused by the novel SARS-CoV-2 coronavirus, represents the greatest global health threat. Most people infected by the virus present mild to moderate respiratory symptoms and recover with supportive treatments. However, certain susceptible hosts develop an acute respiratory distress syndrome (ARDS), associated with an inflammatory "cytokine storm", leading to lung damage. Despite the current availability of different COVID-19 vaccines, the new emerging SARS-CoV-2 genetic variants represent a major concern worldwide, due to their increased transmissibility and rapid spread. Indeed, it seems that some mutations or combinations of mutations might confer selective advantages to the virus, such as the ability to evade the host immune responses elicited by COVID-19 vaccines. Several therapeutic approaches have been investigated but, to date, a unique and fully effective therapeutic protocol has not yet been achieved. In addition, steroid-based therapies, aimed to reduce inflammation in patients with severe COVID-19 disease, may increase the risk of opportunistic infections, increasing the hospitalization time and mortality rate of these patients. Hence, there is an unmet need to develop more effective therapeutic options. Here, we discuss the potential use of natural immunomodulators such as Thymosin α1 (Tα1), all-trans retinoic acid (ATRA), and lactoferrin (LF), as adjunctive or preventive treatment of severe COVID-19 disease. These agents are considered to be multifunctional molecules because of their ability to enhance antiviral host immunity and restore the immune balance, depending on the host immune status. Furthermore, they are able to exert a broad-spectrum antimicrobial activity by means of direct interactions with cellular or molecular targets of pathogens or indirectly by increasing the host immune response. Thus, due to the aforementioned properties, these agents might have a great potential in a clinical setting, not only to counteract SARS-CoV-2 infection, but also to prevent opportunistic infections in critically ill COVID-19 patients.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/imunologia , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Humanos , Fatores Imunológicos/farmacologia , Lactoferrina/imunologia , Lactoferrina/farmacologia , Lactoferrina/uso terapêutico , Tretinoína/imunologia , Tretinoína/farmacologia , Tretinoína/uso terapêutico
11.
Front Immunol ; 12: 550670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34040600

RESUMO

Hibiscus sabdariffa calyx (HS) water decoction extract is a commonly consumed beverage with various pharmacological properties. This systematic review examines the possible effect of HS intake on immune mediators. The Scopus and PUBMED databases were searched for all human and animal studies that investigated the effect of HS administration on immune related biomarkers. For each of the immune biomarkers, the mean, standard deviation and number of subjects were extracted for both the HS treated and untreated group. These values were used in the computation of standardized mean difference (SMD). Statistical analysis and forest plot were done with R statistical software (version 3.6.1). Twenty seven (27) studies met the eligibility criteria. Twenty two (22) of the studies were used for the meta-analysis which included a total of 1211 subjects. The meta-analysis showed that HS administration significantly lowered the levels of TNF-α (n=10; pooled SMD: -1.55; 95% CI: -2.43, -0.67; P < 0.01), IL-6 (n=11; pooled SMD:-1.09; 95% CI: -1.77, -0.40; P < 0.01), IL-1ß (n=7; pooled SMD:-0.62; 95% CI: -1.25, 0.00; P = 0.05), Edema formation (n=4; pooled SMD: -2.29; 95% CI: -4.47, -0.11; P = 0.04), Monocyte Chemoattractant Protein -1 (n=4; pooled SMD: -1.17; 95% CI: -1.78, -0.57; P < 0.01) and Angiotensin converting enzyme cascade (n=6; pooled SMD: -0.91; 95% CI: -1.57, -0.25; P < 0.01). The levels of IL-10 (n=4; pooled SMD: -0.38; 95% CI: -1.67, 0.91; P = 0.56), Interleukin 8 (n=2; pooled SMD:-0.12; 95% CI: -0.76, 0.51; P = 0.71), iNOS (n=2; pooled SMD:-0.69; 95% CI: -1.60, 0.23 P = 0.14) and C- Reactive Protein (n=4; pooled SMD: 0.05; 95% CI: -0.26, 0.36; P = 0.75), were not significantly changed by HS administration. Some of the results had high statistical heterogeneity. HS may be promising in the management of disorders involving hyperactive immune system or chronic inflammation.


Assuntos
Hibiscus/química , Doenças do Sistema Imunitário/prevenção & controle , Imunidade/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Proteína C-Reativa/metabolismo , Citocinas/metabolismo , Humanos , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/metabolismo , Imunidade/imunologia , Fatores Imunológicos/administração & dosagem , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/administração & dosagem
12.
Lung ; 199(3): 239-248, 2021 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1245631

RESUMO

BACKGROUND: To date, only dexamethasone has been shown to reduce mortality in coronavirus disease-19 (COVID-19) patients. Tocilizumab has been recently added to the treatment guidelines for hospitalized COVID-19 patients, but data remain conflicting. STUDY DESIGN AND METHODS: Electronic databases such as MEDLINE, EMBASE, and Cochrane central were searched from March 1, 2020, until March 10, 2021, for randomized controlled trials evaluating the efficacy of tocilizumab in hospitalized COVID-19 patients. The outcomes assessed were all-cause mortality, mechanical ventilation, and time to discharge. RESULTS: Nine studies (with 6490 patients) were included in the analysis. In total, 3358 patients received tocilizumab, and 3132 received standard care/placebo. Pooled analysis showed a significantly decreased risk of all-cause mortality (RR 0.89, 95% CI 0.80-0.98, p = 0.02) and progression to mechanical ventilation (RR 0.80, 95% CI 0.71-0.89, p < 0.0001) in the tocilizumab arm compared to standard therapy or placebo. In addition, there was a trend towards improved median time to hospital discharge (RR 1.28, 95% CI 1.12-1.45, p = 0.0002). CONCLUSIONS: Tocilizumab therapy improves outcomes of mortality and need for mechanical ventilation, in hospitalized patients with COVID-19 infection compared with standard therapy or placebo. Our findings suggest the efficacy of tocilizumab therapy in hospitalized COVID-19 patients and strengthen the concept that tocilizumab is a promising therapeutic intervention to improve mortality and morbidity in COVID-19 patients.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , COVID-19 , Receptores de Interleucina-6/antagonistas & inibidores , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/mortalidade , Humanos , Fatores Imunológicos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , SARS-CoV-2
13.
Eur J Pharmacol ; 905: 174191, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: covidwho-1230459

RESUMO

Azithromycin, a member of the macrolide family of antibiotics, is commonly used to treat respiratory bacterial infections. Nevertheless, multiple pharmacological effects of the drug have been revealed in several investigations. Conceivably, the immunomodulatory properties of azithromycin are among its critical features, leading to its application in treating inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Additionally, azithromycin may directly inhibit viral load as well as its replication, or it could demonstrate indirect inhibitory impacts that might be associated with the expression of antiviral genes. Currently, coronavirus disease 2019 (COVID-19) is an extra urgent issue affecting the entire world, and it is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute respiratory distress syndrome (ARDS), which is associated with hyper inflammation due to cytokine release, is among the leading causes of death in COVID-19 patients with critical conditions. The present paper aims to review the immunomodulatory and antiviral properties of azithromycin as well as its potential clinical applications in the management of COVID-19 patients.


Assuntos
Azitromicina/farmacologia , COVID-19 , Antivirais/farmacologia , COVID-19/tratamento farmacológico , COVID-19/imunologia , Humanos , Fatores Imunológicos/farmacologia , SARS-CoV-2
14.
Clin Nutr ESPEN ; 43: 39-48, 2021 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1157201

RESUMO

BACKGROUND: The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. METHODS: Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. RESULTS: The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. CONCLUSION: There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups.


Assuntos
COVID-19/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Fatores Imunológicos/uso terapêutico , Oligoelementos/uso terapêutico , Vitaminas/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , COVID-19/imunologia , Comorbidade , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Fatores Imunológicos/farmacologia , Masculino , Micronutrientes/farmacologia , Micronutrientes/uso terapêutico , Estado Nutricional , Pandemias , Gravidez , SARS-CoV-2 , Selênio/farmacologia , Selênio/uso terapêutico , Suíça , Oligoelementos/farmacologia , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitaminas/farmacologia , Zinco/farmacologia , Zinco/uso terapêutico
15.
Clin Nutr ESPEN ; 43: 39-48, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34024545

RESUMO

BACKGROUND: The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. METHODS: Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. RESULTS: The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. CONCLUSION: There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups.


Assuntos
COVID-19/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Fatores Imunológicos/uso terapêutico , Oligoelementos/uso terapêutico , Vitaminas/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , COVID-19/imunologia , Comorbidade , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Fatores Imunológicos/farmacologia , Masculino , Micronutrientes/farmacologia , Micronutrientes/uso terapêutico , Estado Nutricional , Pandemias , Gravidez , SARS-CoV-2 , Selênio/farmacologia , Selênio/uso terapêutico , Suíça , Oligoelementos/farmacologia , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitaminas/farmacologia , Zinco/farmacologia , Zinco/uso terapêutico
16.
Food Chem ; 358: 129883, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33940295

RESUMO

Lentinus edodes, an important edible mushroom cultivated in East Asia for thousands of years, has been widely used as food and medicinal ingredient worldwide. Modern phytochemistry studies have demonstrated that L. edodes is very rich in bioactive polysaccharides, especially the ß-glucans. Over the past two decades, the isolation, chemical properties, and bioactivities of polysaccharides from fruiting bodies, mycelium and fermentation broth of L. edodes have been drawing much attention from scholars around the world. It has been demonstrated that L. edodes polysaccharides possess various remarkable biological activities, including anti-oxidant, anti-tumor, anti-aging, anti-inflammation, immunomodulatory, antiviral, and hepatoprotection effects. This review summarizes the recent development of polysaccharides from L. edodes including the isolation methods, structural features, bioactivities and mechanisms, and their structure-activity relationship, which can provide useful research underpinnings and update information for their further application as therapeutic agents and functional foods.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Cogumelos Shiitake/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/química , Antioxidantes/química , Antivirais/química , Antivirais/farmacologia , Alimento Funcional , Polissacarídeos Fúngicos/isolamento & purificação , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Micélio/química , Relação Estrutura-Atividade , beta-Glucanas/química , beta-Glucanas/farmacologia
17.
Eur J Pharmacol ; 905: 174191, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34015317

RESUMO

Azithromycin, a member of the macrolide family of antibiotics, is commonly used to treat respiratory bacterial infections. Nevertheless, multiple pharmacological effects of the drug have been revealed in several investigations. Conceivably, the immunomodulatory properties of azithromycin are among its critical features, leading to its application in treating inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Additionally, azithromycin may directly inhibit viral load as well as its replication, or it could demonstrate indirect inhibitory impacts that might be associated with the expression of antiviral genes. Currently, coronavirus disease 2019 (COVID-19) is an extra urgent issue affecting the entire world, and it is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute respiratory distress syndrome (ARDS), which is associated with hyper inflammation due to cytokine release, is among the leading causes of death in COVID-19 patients with critical conditions. The present paper aims to review the immunomodulatory and antiviral properties of azithromycin as well as its potential clinical applications in the management of COVID-19 patients.


Assuntos
Azitromicina/farmacologia , COVID-19 , Antivirais/farmacologia , COVID-19/tratamento farmacológico , COVID-19/imunologia , Humanos , Fatores Imunológicos/farmacologia , SARS-CoV-2
18.
BMC Complement Med Ther ; 21(1): 141, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980308

RESUMO

BACKGROUND: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections. METHODS: Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes. RESULTS: Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections. CONCLUSIONS: Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense.


Assuntos
COVID-19/tratamento farmacológico , Echinacea , Fatores Imunológicos/farmacologia , Monócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Interferons/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico
19.
Lung ; 199(3): 239-248, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34050796

RESUMO

BACKGROUND: To date, only dexamethasone has been shown to reduce mortality in coronavirus disease-19 (COVID-19) patients. Tocilizumab has been recently added to the treatment guidelines for hospitalized COVID-19 patients, but data remain conflicting. STUDY DESIGN AND METHODS: Electronic databases such as MEDLINE, EMBASE, and Cochrane central were searched from March 1, 2020, until March 10, 2021, for randomized controlled trials evaluating the efficacy of tocilizumab in hospitalized COVID-19 patients. The outcomes assessed were all-cause mortality, mechanical ventilation, and time to discharge. RESULTS: Nine studies (with 6490 patients) were included in the analysis. In total, 3358 patients received tocilizumab, and 3132 received standard care/placebo. Pooled analysis showed a significantly decreased risk of all-cause mortality (RR 0.89, 95% CI 0.80-0.98, p = 0.02) and progression to mechanical ventilation (RR 0.80, 95% CI 0.71-0.89, p < 0.0001) in the tocilizumab arm compared to standard therapy or placebo. In addition, there was a trend towards improved median time to hospital discharge (RR 1.28, 95% CI 1.12-1.45, p = 0.0002). CONCLUSIONS: Tocilizumab therapy improves outcomes of mortality and need for mechanical ventilation, in hospitalized patients with COVID-19 infection compared with standard therapy or placebo. Our findings suggest the efficacy of tocilizumab therapy in hospitalized COVID-19 patients and strengthen the concept that tocilizumab is a promising therapeutic intervention to improve mortality and morbidity in COVID-19 patients.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , COVID-19 , Receptores de Interleucina-6/antagonistas & inibidores , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/mortalidade , Humanos , Fatores Imunológicos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , SARS-CoV-2
20.
Expert Opin Biol Ther ; 21(5): 675-686, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33835886

RESUMO

Objective: Efficacy and safety of Itolizumab, an immunomodulatory mAb, in treating moderate-to-severe acute respiratory distress syndrome (ARDS) due to cytokine release in COVID-19 patients was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase-2 study.Methods: Patients were randomized (2:1) to Arm-A (best supportive care [BSC]+Itolizumab) and Arm-B (BSC). Primary outcome of interest was reduction in mortality 30-days after enrollment.Results: Thirty-six patients were screened, five treated as first-dose-sentinels and rest randomized, while four patients were screen-failures. Two patients in Arm-A discontinued prior to receiving one complete infusion and were replaced. At end of 1-month, there were three deaths in Arm-B, and none in Arm-A (p = 0.0296; 95% CI = -0.3 [-0.61, -0.08]). At end of study, more patients in Arm-A had improved SpO2 without increasing FiO2 (p = 0.0296), improved PaO2 (p = 0.0296), and reduction in IL-6 (43 vs 212 pg/ml; p = 0.0296) and tumor necrotic factor-α (9 vs 39 pg/ml; p = 0.0253) levels. Transient lymphopenia (Arm-A: 11 patients) and infusion reactions (7 patients) were commonly reported treatment-related safety events.Conclusion: Itolizumab is a promising, safe and effective immunomodulatory therapy for treatment of ARDS due to cytokine release in COVID-19 patients, with survival and recovery-benefit.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Índice de Gravidade de Doença , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , COVID-19/complicações , COVID-19/imunologia , Feminino , Humanos , Fatores Imunológicos/farmacologia , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/imunologia , SARS-CoV-2/imunologia , Resultado do Tratamento
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