RESUMO
AIM: Metronidazole (MTZ) is an antimicrobial agent used to treat anaerobic infections. It has been hypothesized that MTZ may also have anti-inflammatory properties, but the evidence is limited and has not been previously reviewed. Thus, this scoping review aimed to answer the following question: "What is the evidence supporting anti-inflammatory properties of metronidazole that are not mediated by its antimicrobial effects?" METHODS: A scoping review was conducted according to the PRISMA-ScR statement. Five databases were searched up to January 2023 for studies evaluating the anti-inflammatory properties of MTZ used as monotherapy for treating infectious and inflammatory diseases. RESULTS: A total of 719 records were identified, and 27 studies (21 in vivo and 6 in vitro) were included. The studies reported experimental evidence of MTZ anti-inflammatory effects on (1) innate immunity (barrier permeability, leukocyte adhesion, immune cell populations), (2) acquired immunity (lymphocyte proliferation, T-cell function, cytokine profile), and (3) wound healing/resolution of inflammation. CONCLUSION: Taken together, this scoping review supported a potential anti-inflammatory effect of MTZ in periodontitis treatment. We recommend that future clinical studies should be conducted to evaluate specific MTZ anti-inflammatory pathways in the treatment of periodontitis.
Assuntos
Anti-Inflamatórios , Metronidazol , Periodontite , Metronidazol/uso terapêutico , Metronidazol/farmacologia , Humanos , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Animais , Imunidade Inata/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Imunidade Adaptativa/efeitos dos fármacos , Inflamação/tratamento farmacológicoRESUMO
The innate and acquired immune response induced by a commercial inactivated vaccine against Bovine Herpesvirus-1 (BoHV-1) and protection conferred against the virus were analyzed in cattle. Vaccination induced high levels of BoHV-1 antibodies at 30, 60, and 90 days post-vaccination (dpv). IgG1 and IgG2 isotypes were detected at 90 dpv, as well as virus-neutralizing antibodies. An increase of anti-BoHV-1 IgG1 in nasal swabs was detected 6 days post-challenge in vaccinated animals. After viral challenge, lower virus excretion and lower clinical score were observed in vaccinated as compared to unvaccinated animals, as well as BoHV-1-specific proliferation of lymphocytes and production of IFNγ, TNFα, and IL-4. Downregulation of the expression of endosome Toll-like receptors 8-9 was detected after booster vaccination. This is the first thorough study of the immunity generated by a commercial vaccine against BoHV-1 in cattle.
Assuntos
Anticorpos Neutralizantes/biossíntese , Herpesvirus Bovino 1/imunologia , Vacinas contra Herpesvirus/administração & dosagem , Imunoglobulina G/biossíntese , Rinotraqueíte Infecciosa Bovina/prevenção & controle , Receptor 8 Toll-Like/imunologia , Receptor Toll-Like 9/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Anticorpos Antivirais , Bovinos , Proliferação de Células , Endossomos/imunologia , Endossomos/metabolismo , Expressão Gênica , Herpesvirus Bovino 1/patogenicidade , Imunidade Inata/efeitos dos fármacos , Imunização Secundária/métodos , Rinotraqueíte Infecciosa Bovina/genética , Rinotraqueíte Infecciosa Bovina/imunologia , Rinotraqueíte Infecciosa Bovina/virologia , Interferon gama/genética , Interferon gama/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Linfócitos/imunologia , Linfócitos/virologia , Masculino , Cavidade Nasal/imunologia , Cavidade Nasal/virologia , Receptor 8 Toll-Like/agonistas , Receptor 8 Toll-Like/genética , Receptor Toll-Like 9/agonistas , Receptor Toll-Like 9/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Vacinação/métodos , Vacinas de Produtos InativadosRESUMO
Furazolidone (FZD) is a widely used drug in human and veterinary medicine, and has antibacterial and antiprotozoal action. Although it is widely used as a therapy in various pathological conditions, studies on the efficacy of FZD associated with immune responses are still limited. In this review, we seek to describe which immunopharmacological responses are caused by the administration of FZD. The study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A systematic review of clinical trials and in vitro and in vivo experimental studies was carried out, which resulted in 943 papers, of which 35 were considered eligible and, of these 35, 4 were selected for analysis. The studies listed indicated that administration of FZD can modulate pro- or anti-inflammatory pathways, with a probable increase in the expression of reactive oxygen species and a modulation of apoptotic pathways.
Assuntos
Imunidade Adaptativa/imunologia , Anti-Infecciosos Locais/farmacologia , Apoptose/imunologia , Furazolidona/farmacologia , Imunidade Inata/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Currently there is increasing attention on the modulatory effects of benzodiazepines on the immune system. Here, we evaluate how Diazepam (DZ) affects both innate and adaptive immunity. We observed that treatment with DZ and Lipopolysaccharide (LPS) on macrophages or dendritic cells (DCs) induced a defective secretion of IL-12, TNF-α, IL-6 and a lesser expression of classical activation markers as NO production and CD40 in comparison with LPS condition. More importantly, mice pre-treated with DZ and then challenged to LPS induced-septic shock showed reduced death. The DZ treatment shifted the LPS-induced pro-inflammatory cytokine production of peritoneal cells (PCs) to an anti-inflammatory profile commanded by IL-10. In agreement with this, DZ treatment prevented LPS-induced DC ability to initiate allogeneic Th1 and Th17 responses in vitro when compared with LPS-matured DC. Since these inflammatory responses are the key in the development of the experimental autoimmune encephalomyelitis (EAE), we treated EAE mice preventively with DZ. Mice that received DZ showed amelioration of clinical signs and immunological parameters of the disease. Additionally, DZ reduced the release of IFN-γ and IL-17 by splenocytes from untreated sick mice in vitro. For this reason, we decided to treat diseased mice therapeutically with DZ when they reached the clinical score of 1. Most importantly, this treatment ameliorated clinical signs, reduced the MOG-specific inflammatory cytokine production and prevented axonal damage. Altogether, these results indicate that DZ is a potent immunomodulator capable of controlling undesired innate and adaptive immune responses, both at the beginning of these responses and also once they have started.
Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Diazepam/farmacologia , Encefalomielite Autoimune Experimental/imunologia , Imunidade Inata/efeitos dos fármacos , Imunomodulação/efeitos dos fármacos , Animais , Biomarcadores , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/diagnóstico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Feminino , Imunofenotipagem , Lipopolissacarídeos/efeitos adversos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Índice de Gravidade de Doença , Choque Séptico/tratamento farmacológico , Choque Séptico/etiologia , Choque Séptico/metabolismo , Choque Séptico/mortalidadeRESUMO
We aimed to investigate the effects of ethanol and its metabolites (ß-hydroxybutyrate and sodium acetate) in the effector functions of macrophages in response to Paracoccidioides brasiliensis yeast cells and to determine their influence in the development of the adaptive response. Purified peripheral blood monocytes were differentiated into macrophages and were treated with ethanol, ß-hydroxybutyrate, and sodium acetate, and stimulated with P. brasiliensis yeast cells and evaluated for their phenotypic characteristics, functional activity, and capability to induce T cells activation/differentiation. We found that the ethanol treatment diminished the expression of HLA-AB, HLA-DR, CD80, and CD86, modulating the expression of dectin-1, as well as Syk phosphorylation. The ethanol treatment increased the phagocytic activity, expression of CD206, and IL-10 production; however, reduced ROS production, fungicidal activity, caspase-1 cleavage, and IL-1ß and IL-6 production. Our data also showed that the presence of ethanol reduced the differentiation of Th1 and Th17 cells and increased the frequency of Th2 cells. Our results indicated that ethanol exposure could suppress effector function of macrophages, possibly leading to the polarization of M2 macrophages. The ethanol modulates the expression of costimulatory and antigen-presentation molecules and interferes with the NLRP3 inflammasome. Altogether, these alterations affect the development of the adaptive response, decreasing the frequency of IL-17, IL-22, and IFN- γ producing cells, and increasing the frequency of IL-4 producing cells. Therefore, exposure to ethanol can impair the capability of macrophages to exert their effector functions and activate the acquired response related to resistance to P. brasiliensis infection.
Assuntos
Etanol/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Paracoccidioides/fisiologia , Paracoccidioidomicose/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Antifúngicos/farmacologia , Complexo CD3/análise , Caspase 1/análise , Citocinas/análise , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Receptores de Lipopolissacarídeos/análise , Macrófagos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peróxidos/metabolismo , Fagocitose/efeitos dos fármacosAssuntos
Antivirais/farmacologia , Betacoronavirus , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral , Glicoproteína da Espícula de Coronavírus/metabolismo , Imunidade Adaptativa/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Descoberta de Drogas , Humanos , Pulmão/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores Virais/metabolismo , SARS-CoV-2 , Resultado do Tratamento , Internalização do Vírus/efeitos dos fármacosRESUMO
BACKGROUND: Pathogens use multiple mechanisms to disrupt cell functioning in their host and allow pathogenesis. These mechanisms involve communication between the pathogen and the host cell through protein-protein interactions. METHODS: Protein-protein interactions chains referred to as signal transduction pathways are the processes by which a chemical or physical signal transmits through a cell as series of molecular events so the pathogen needs to intercept these molecular pathways at few positions to induce pathogenesis such as pathogen viability, infection or hypersensitivity. RESULTS: The pathogen nodes of interception are not necessarily the most immunogenic; so that novel immunogenicity-improvement strategies need to be developed thought a chemical conjugation of the pathogen-carrier nodes to develop an efficient immune response in order to block pathogenesis. On the other hand, if pathogen-carriers are immunogens; toleration ought to be induced by this conjugation avoiding hypersensitivity. Thus, this paper addresses the biological plausibility of plant-phenolics as pathogen-carrier immunogenicity modulator haptens. CONCLUSION: The plant-phenolic compounds have in their structure functional groups such as hydroxyl, carbonyl, carboxyl, ester, or ether, capable of reacting with the amino or carbonyl groups of the amino acids of a pathogen-carrier to form conjugates. Besides, the varied carbon structures these phenolic compounds have; it is possible to alter the pathogen-carrier related factors that determine the immunogenicity: 1) Structural complexity, 2) Molecular size, 3) Structural heterogeneity, 4) Accessibility to antigenic determinants or epitopes, 5) Optical configuration, 6) Physical state, or 7) Molecular rigidity.
Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Haptenos/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata/efeitos dos fármacos , Fenóis/imunologia , Plantas/imunologia , Imunidade Adaptativa/imunologia , Aminoácidos/química , Aminoácidos/imunologia , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/imunologia , Humanos , Imunidade Inata/imunologia , Fenóis/química , Plantas/química , Transdução de SinaisRESUMO
BACKGROUND: Boron is considered a trace element that induces various effects in systems of the human body. However, each boron-containing compound exerts different effects. OBJECTIVE: To review the effects of 2-Aminoethyldiphenyl borinate (2-APB), an organoboron compound, on the human body, but also, its effects in animal models of human disease. METHODS: In this review, the information to showcase the expansion of these reported effects through interactions with several ion channels and other receptors has been reported. These effects are relevant in the biomedical and chemical fields due to the application of the reported data in developing therapeutic tools to modulate the functions of the immune, cardiovascular, gastrointestinal and nervous systems. RESULTS: Accordingly, 2-APB acts as a modulator of adaptive and innate immunity, including the production of cytokines and the migration of leukocytes. Additionally, reports show that 2-APB exerts effects on neurons, smooth muscle cells and cardiomyocytes, and it provides a cytoprotective effect by the modulation and attenuation of reactive oxygen species. CONCLUSION: The molecular pharmacology of 2-APB supports both its potential to act as a drug and the desirable inclusion of its moieties in new drug development. Research evaluating its efficacy in treating pain and specific maladies, such as immune, cardiovascular, gastrointestinal and neurodegenerative disorders, is scarce but interesting.
Assuntos
Compostos de Boro/uso terapêutico , Pró-Fármacos/uso terapêutico , Ativação Metabólica , Imunidade Adaptativa/efeitos dos fármacos , Compostos de Boro/química , Compostos de Boro/farmacologia , Cálcio/metabolismo , Sistema Cardiovascular/efeitos dos fármacos , Sistema Digestório/efeitos dos fármacos , Humanos , Imunidade Inata/efeitos dos fármacos , Modelos Moleculares , Estrutura Molecular , Miócitos Cardíacos/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Sistema Nervoso/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Canais de Cátion TRPV/química , Canais de Cátion TRPV/metabolismoRESUMO
BACKGROUND: The immune system is responsible for providing protection to the body against foreign substances. The immune system divides into two types of immune responses to study its mechanisms of protection: 1) Innate and 2) Adaptive. The innate immune response represents the first protective barrier of the organism that also works as a regulator of the adaptive immune response, if evaded the mechanisms of the innate immune response by the foreign substance the adaptive immune response takes action with the consequent antigen neutralization or elimination. The adaptive immune response objective is developing a specific humoral response that consists in the production of soluble proteins known as antibodies capable of specifically recognizing the foreign agent; such protective mechanism is induced artificially through an immunization or vaccination. Unfortunately, the immunogenicity of the antigens is an intrinsic characteristic of the same antigen dependent on several factors. CONCLUSION: Vaccine adjuvants are chemical substances of very varied structure that seek to improve the immunogenicity of antigens. The main four types of adjuvants under investigation are the following: 1) Oil emulsions with an antigen in solution, 2) Pattern recognition receptors activating molecules, 3) Inflammatory stimulatory molecules or activators of the inflammasome complex, and 4) Cytokines. However, this paper addresses the biological plausibility of two phytochemical compounds as vaccine adjuvants: 5) Lectins, and 6) Plant phenolics whose characteristics, mechanisms of action and disadvantages are addressed. Finally, the immunological usefulness of these molecules is discussed through immunological data to estimate effects of plant phenolics and lectins as vaccine adjuvants, and current studies that have implanted these molecules as vaccine adjuvants, demonstrating the results of this immunization.
Assuntos
Adjuvantes Imunológicos/farmacologia , Lectinas/farmacologia , Plantas/química , Polifenóis/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Adjuvantes Imunológicos/isolamento & purificação , Animais , Antígenos/imunologia , Citocinas/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Lectinas/imunologia , Lectinas/isolamento & purificação , Polifenóis/imunologia , Polifenóis/isolamento & purificação , Vacinação/métodos , Vacinas/imunologiaRESUMO
Psoriasis is a chronic, recurrent, immune-mediated, hyperproliferative inflammatory skin disease. The role of the adaptive immune system, particularly of Th1 and Th17 lymphocytes, has been regarded as prominent in the immunopathogenesis of psoriasis, as well as decreased Tregs function. Immunobiological drugs were administered in therapeutic pulses and a few studies evaluate their effects on the immune repertoire. The aim of this study was to evaluate the adaptive immune profile of patients with severe psoriasis under immunobiological treatment in two time points. Thirty-two psoriasis patients and 10 control patients were evaluated. In the group of psoriasis patients, 10 patients were on anti-TNF and 14 patients on methotrexate treatment, while 8 individuals were not treated. IL-17, IFN-γ, TNF-α, IL-6, IL-2, and IL-10 were analyzed. CD4 T cell intracellular cytokines were analyzed. It was observed that stimulation could significantly increase the production of IL-17, IFN-γ, TNF-α, and IL-10 only before anti-TNF pulse therapy. The activation of Th1 and Treg cells after stimulation was significantly higher before anti-TNF pulse. Patients on methotrexate or anti-TNF therapy produced significantly lower levels of TNF-α, IL-10, and IL-6. Furthermore, these patients showed a significant decrease in the activated CD4+ T cells. The treatment with immunomodulator or methotrexate modulates the activation of CD4+ T cells, and anti-TNF treatment appears to have a modulating effect on the activation and production of Th1, Th17, and Treg cells.