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2.
Lancet Oncol ; 21(9): e419-e430, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32888471

RESUMO

Notable advances have been achieved in the treatment of cancer since the advent of immunotherapy, and immune checkpoint inhibitors have shown clinical benefit across a wide variety of tumour types. Nevertheless, most patients still progress on these treatments, highlighting the importance of unravelling the underlying mechanisms of primary resistance to immunotherapy. A well described biomarker of non-responsiveness to immune checkpoint inhibitors is the absence or low presence of lymphocytes in the tumour microenvironment, so-called cold tumours. There are five mechanisms of action that have the potential to turn cold tumours into so-called hot and inflamed tumours, hence increasing the tumour's responsiveness to immunotherapy-increasing local inflammation, neutralising immunosuppression at the tumour site, modifying the tumour vasculature, targeting the tumour cells themselves, or increasing the frequency of tumour-specific T cells. In this Review, we discuss preclinical data that serves as the basis for ongoing immunotherapy clinical trials for the treatment of non-immunoreactive tumours, as well as reviewing clinical and translational data where available. We explain how improving our understanding of the underlying mechanisms of primary resistance to immunotherapy will help elucidate an increasingly granular view of the tumour microenvironment cellular composition, functional status, and cellular localisation, with the goal of further therapy refinement.


Assuntos
Resistencia a Medicamentos Antineoplásicos/imunologia , Imunoterapia/efeitos adversos , Inflamação/terapia , Neoplasias/terapia , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Quinase 1 do Ponto de Checagem/antagonistas & inibidores , Quinase 1 do Ponto de Checagem/imunologia , Ensaios Clínicos como Assunto , Humanos , Imunidade Celular/imunologia , Inflamação/imunologia , Inflamação/patologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Microambiente Tumoral/imunologia
3.
Paediatr Respir Rev ; 35: 81-87, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32792288

RESUMO

The rapid spread of SARS-CoV-2 infection globally coupled with the relatively high case-fatality rate has led to immediate need for therapeutic intervention to prevent and treat COVID-19 disease. There is accumulating evidence that morbidity and mortality in COVID-19 may be exacerbated by a dysregulated host immune response resulting in significant hyperinflammation and cytokine release. The aim of this review is to describe the basis for the immune dysregulation caused by SARS-CoV-2 infection and to examine current investigations into immunomodulatory therapies aimed at targeting the excessive host immune response.


Assuntos
Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Corticosteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Complexo Antígeno-Anticorpo/imunologia , Betacoronavirus , Criança , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/fisiopatologia , Síndrome da Liberação de Citocina/terapia , Humanos , Imunização Passiva/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Inflamação/imunologia , Inflamação/fisiopatologia , Inflamação/terapia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Pandemias , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Receptores de Interleucina-6/antagonistas & inibidores , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/terapia
4.
Life Sci ; 258: 118166, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739471

RESUMO

In this paper, a model is proposed of the pathophysiological processes of COVID-19 starting from the infection of human type II alveolar epithelial cells (pneumocytes) by SARS-CoV-2 and culminating in the development of ARDS. The innate immune response to infection of type II alveolar epithelial cells leads both to their death by apoptosis and pyroptosis and to alveolar macrophage activation. Activated macrophages secrete proinflammatory cytokines and chemokines and tend to polarise into the inflammatory M1 phenotype. These changes are associated with activation of vascular endothelial cells and thence the recruitment of highly toxic neutrophils and inflammatory activated platelets into the alveolar space. Activated vascular endothelial cells become a source of proinflammatory cytokines and reactive oxygen species (ROS) and contribute to the development of coagulopathy, systemic sepsis, a cytokine storm and ARDS. Pulmonary activated platelets are also an important source of proinflammatory cytokines and ROS, as well as exacerbating pulmonary neutrophil-mediated inflammatory responses and contributing to systemic sepsis by binding to neutrophils to form platelet-neutrophil complexes (PNCs). PNC formation increases neutrophil recruitment, activation priming and extraversion of these immune cells into inflamed pulmonary tissue, thereby contributing to ARDS. Sequestered PNCs cause the development of a procoagulant and proinflammatory environment. The contribution to ARDS of increased extracellular histone levels, circulating mitochondrial DNA, the chromatin protein HMGB1, decreased neutrophil apoptosis, impaired macrophage efferocytosis, the cytokine storm, the toll-like receptor radical cycle, pyroptosis, necroinflammation, lymphopenia and a high Th17 to regulatory T lymphocyte ratio are detailed.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Células Epiteliais Alveolares/imunologia , Células Epiteliais Alveolares/patologia , Animais , Betacoronavirus/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Humanos , Imunidade Inata , Inflamação/etiologia , Inflamação/imunologia , Inflamação/fisiopatologia , Inflamação/terapia , Ativação de Macrófagos , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/patologia , Ativação de Neutrófilo , Pandemias , Ativação Plaquetária , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Trombofilia/etiologia , Trombofilia/imunologia , Trombofilia/fisiopatologia , Trombofilia/terapia
5.
Cell Transplant ; 29: 963689720952089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32830527

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic, originating from Wuhan, China, is known to cause severe acute respiratory symptoms. The occurrence of a cytokine storm in the lungs is a critical step in the disease pathogenesis, as it causes pathological lesions, pulmonary edema, and acute respiratory distress syndrome, potentially resulting in death. Currently, there is no effective treatment that targets the cytokine storm and helps regenerate the damaged tissue. Mesenchymal stem cells (MSCs) are known to act as anti-inflammatory/immunomodulatory candidates and activate endogenous regeneration. As a result, MSC therapy is a potential treatment approach for COVID-19. Intravenous injection of clinical-grade MSCs into COVID-19 patients can induce an immunomodulatory response along with improved lung function. Dental pulp stem cells (DPSCs) are considered a potential source of MSCs for immunomodulation, tissue regeneration, and clinical application. Although some current clinical trials have treated COVID-19 patients with DPSCs, this therapy has not been approved. Here, we review the potential use of DPSCs and their significance in the development of a therapy for COVID-19.


Assuntos
Infecções por Coronavirus/terapia , Polpa Dentária/citologia , Imunomodulação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Pneumonia Viral/terapia , Betacoronavirus/imunologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Polpa Dentária/imunologia , Humanos , Imunoterapia/métodos , Inflamação/imunologia , Inflamação/terapia , Pulmão/imunologia , Pulmão/fisiologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/terapia , Células-Tronco Mesenquimais/citologia , Pandemias , Pneumonia Viral/imunologia , Regeneração
6.
Z Rheumatol ; 79(7): 679-685, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32757030

RESUMO

A few days after the SARS-CoV-2 infection was declared a pandemic, the German Society for Rheumatology (DGRh) compiled first recommendations for the care of patients with inflammatory rheumatic diseases (IRD). These first recommendations were based on an expert consensus and were largely non-evidence-based. Now that the first scientific data from registers, cross-sectional studies, case reports and case series are available, the present update is intended to update the previous recommendations and to add new findings. The current recommendations are based on a literature search of publications available up to 15 June 2020 and address preventive measures (such as hygiene measures or vaccinations) and the use of immunomodulatory/immunosuppressive drugs. An important goal of the current recommendations is also to prevent harm to patients with IRD through unjustified restriction of care. The DGRh will continue to update its recommendations in the case of new aspects and will publish them as well as further information on the COVID-19 pandemic on its homepage ( www.dgrh.de ) in an ongoing process.


Assuntos
Infecções por Coronavirus/epidemiologia , Inflamação/terapia , Pneumonia Viral/epidemiologia , Doenças Reumáticas/terapia , Reumatologia/métodos , Betacoronavirus , Alemanha , Humanos , Pandemias , Sociedades Médicas
7.
Z Rheumatol ; 79(7): 686-691, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32845393

RESUMO

The recommendations of the German Society of Rheumatology (DGRh) update, which update and expand the guidance on the management of patients with inflammatory rheumatic diseases in view of SARS-CoV­2 created at the beginning of the COVID-19 pandemic, correspond in many points with the recommendations for action of the American (ACR) and European (EULAR) societies, but also differ in some points. Therefore, this article discusses the core recommendations of the DGRh update on the prevention of SARS-CoV-2/COVID-19, the risk assessment for inflammatory rheumatic diseases and the use of antirheumatic treatments in the context and in comparison to the ACR and EULAR recommendations, and provides an overview of the risk assessment of individual antirheumatic drugs.


Assuntos
Antirreumáticos/uso terapêutico , Infecções por Coronavirus/epidemiologia , Inflamação/terapia , Pneumonia Viral/epidemiologia , Doenças Reumáticas/terapia , Reumatologia , Betacoronavirus , Europa (Continente) , Alemanha , Humanos , Pandemias , Guias de Prática Clínica como Assunto , Medição de Risco , Sociedades Médicas , Estados Unidos
8.
Orv Hetil ; 161(35): 1436-1440, 2020 08.
Artigo em Húngaro | MEDLINE | ID: mdl-32822321

RESUMO

Neuropeptides synthetised in the enteric nervous system can change the function of the immunocells and play a role in inflammatory processes. In our review the effects of inflammation on the neuropeptide content of nerves and immune cells were compared. Inflamed tissue samples (human gastritis and animal models with experimental colitis and streptozotocin-induced diabetes mellitus) were examined. The number and contacts of neuropeptide-containing nerves and immune cells were studied using immunohistochemistry, confocal laser microscopy and electronmicroscopy. In inflammation, the number of substance P, vasoactive intestinal polypeptide and neuropeptide Y nerve fibres was increased significantly in parallel with the strongly increased number of immunocompetent cells (p<0.001). In inflammatory diseases, a large number of lymphocytes and mast cells were also positive for these neuropeptides. Very close morphological relationship between substance P and neuropeptide Y immunoreactive nerve fibres and immunocells could be demonstrated only in inflamed mucosa. Some of the substance P immunoreactive immunocells were also immunoreactive for tumor necrosis factor alpha and nuclear factor kappa B in the case of inflammation. The increased number of tumor necrosis factor alpha and nuclear factor kappa B immunoreactive immune cells correlated with the increased number of substance P-containing nerve fibres. Substance P, vasoactive intestinal polypeptide and neuropeptide Y released from nerve fibres and immunocells can play a role in inflammation. Our results suggest that using substance P antagonists or vasoactive intestinal polypeptide and neuropeptide Y peptides might be a novel therapeutic concept in the management of inflammation. Orv Hetil. 2020; 161(35): 1436-1440.


Assuntos
Inflamação/terapia , Neuropeptídeo Y/metabolismo , Substância P/metabolismo , Substância P/uso terapêutico , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Imuno-Histoquímica/métodos , Inflamação/imunologia , Inflamação/metabolismo , Fibras Nervosas/imunologia , Fibras Nervosas/metabolismo , Neuropeptídeo Y/imunologia , Neuropeptídeo Y/uso terapêutico , Substância P/imunologia , Peptídeo Intestinal Vasoativo/imunologia , Peptídeo Intestinal Vasoativo/uso terapêutico
9.
Nat Commun ; 11(1): 3384, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636379

RESUMO

Targeting single mediators has failed to reduce the mortality of sepsis. We developed a telodendrimer (TD) nanotrap (NT) to capture various biomolecules via multivalent, hybrid and synergistic interactions. Here, we report that the immobilization of TD-NTs in size-exclusive hydrogel resins simultaneously adsorbs septic molecules, e.g. lipopolysaccharides (LPS), cytokines and damage- or pathogen-associated molecular patterns (DAMPs/PAMPs) from blood with high efficiency (92-99%). Distinct surface charges displayed on the majority of pro-inflammatory cytokines (negative) and anti-inflammatory cytokines (positive) allow for the selective capture via TD NTs with different charge moieties. The efficacy of NT therapies in murine sepsis is both time-dependent and charge-dependent. The combination of the optimized NT therapy with a moderate antibiotic treatment results in a 100% survival in severe septic mice by controlling both infection and hyperinflammation, whereas survival are only 50-60% with the individual therapies. Cytokine analysis, inflammatory gene activation and tissue histopathology strongly support the survival benefits of treatments.


Assuntos
Dendrímeros/química , Inflamação/terapia , Nanopartículas/química , Sepse/terapia , Adsorção , Animais , Antibacterianos/uso terapêutico , Citocinas/metabolismo , Feminino , Humanos , Hidrogéis , Lipopolissacarídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanomedicina , Padrões Moleculares Associados a Patógenos , Células RAW 264.7
10.
Dtsch Med Wochenschr ; 145(15): 1044-1050, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32731277

RESUMO

Infection with SARS-COV-2 leads to a number of pathologies in the hematopoetic system that have significant impact on clinical symptoms and mortality. There are 3 stages of infection: (1) early upper respiratory tract infection with fever and lymphopenia (2) pulmonary phase and (3) hyperinflammatory phase with the clinical signs of organ failure such as ARDS/shock. Hyperinflammation, which is triggered by activation of T cells and monocytes/macrophages, is essential for organ pathologies. Interferon IFN-É£, tumor necrosis factor (TNF)-α, IL-10 and interleukin-6 (IL-6) play important roles as mediators of inflammation. In analogy to the cytokine release syndrome (CRS) after CAR-T cell therapy, the therapeutic activity of the IL-6 receptor antibody tocilizumab is investigated in clinical studies.The coagulation system is activated during the inflammatory phase of COVID infection, most likely on the pathophysiological basis of immune thrombosis. Clinically, there is a significantly increased incidence of venous (especially pulmonary artery embolism), but also arterial thromboembolism (TE). In laboratory chemistry, the D-dimer, fibrinogen but also vWF and FVIII are significantly increased. Guidelines for the prophylaxis and therapy of COVID-associated coagulopathy have been developed. Analogous to other viral infections, there are approaches to passive immunization using convalescent plasma. Its administration has shown promising activity in first uncontrolled case series and is currently being examined in clinical studies worldwide for its therapeutic activity.


Assuntos
Infecções por Coronavirus , Doenças Hematológicas , Pandemias , Pneumonia Viral , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Embolia/prevenção & controle , Embolia/terapia , Embolia/virologia , Doenças Hematológicas/prevenção & controle , Doenças Hematológicas/terapia , Doenças Hematológicas/virologia , Humanos , Inflamação/prevenção & controle , Inflamação/terapia , Inflamação/virologia , Pneumonia Viral/complicações , Pneumonia Viral/terapia
11.
Biomed Environ Sci ; 33(5): 331-337, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32553077

RESUMO

Objective: Hyperbaric oxygen treatment (HBOT) has demonstrated efficacy in improving hearing levels of patients with idiopathic sudden sensorineural hearing loss (ISSHL); however, the underlying mechanisms are not well understood. HBOT alleviates the inflammatory response, which is mediated by Toll-like receptor (TLR) 4 and nuclear factor (NF)-κB. In this study we investigated whether HBOT attenuates inflammation in ISHHL patients via alteration of TLR4 and NF-κB expression. Methods: ISHHL patients ( n = 120) and healthy control subjects ( n = 20) were enrolled in this study. Patients were randomly divided into medicine group treated with medicine only ( n = 60) and HBO group receiving both HBOT and medicine ( n = 60). Audiometric testing was performed pre- and post-treatment. TLR4, NF-кB, and TNF-α expression in peripheral blood of ISSHL patients and healthy control subjects was assessed by ELISA before and after treatment. Results: TLR4, NF-κB, and TNF-α levels were upregulated in ISSHL patients relative to healthy control subjects; the levels were decreased following treatment and were lower in the HBO group than that in the medicine group post-treatment ( P < 0.05 and P < 0.01). Conclusion: HBOT alleviates hearing loss in ISSHL patients by suppressing the inflammatory response induced by TLR4 and NF-κB signaling.


Assuntos
Perda Auditiva Neurossensorial/terapia , Perda Auditiva Súbita/terapia , Oxigenação Hiperbárica , Inflamação/terapia , Subunidade p50 de NF-kappa B/genética , Receptor 4 Toll-Like/genética , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Adulto Jovem
12.
Am J Physiol Renal Physiol ; 319(1): F125-F138, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32508112

RESUMO

Acute kidney injury (AKI) is an important clinical disorder with high prevalence, serious consequences, and limited therapeutic options. Modulation of neuroimmune interaction by nonpharmacological methods is emerging as a novel strategy for treating inflammatory diseases, including AKI. Recently, pulsed ultrasound (US) treatment was shown to protect from AKI by stimulating the cholinergic anti-inflammatory pathway. Because of the relatively simple, portable, and noninvasive nature of US procedures, US stimulation may be a valuable therapeutic option for treating inflammatory conditions. This review discusses potential impacts of US bioeffects on the nervous system and how this may generate feedback onto the immune system. We also discuss recent evidence supporting the use of US as a means to treat AKI and other inflammatory diseases.


Assuntos
Lesão Renal Aguda/terapia , Neuroimunomodulação , Ultrassonografia de Intervenção/métodos , Humanos , Inflamação/terapia
13.
PLoS One ; 15(6): e0234867, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569300

RESUMO

Different modes of exogenous electrical stimulation at physiological strength has been applied to various diseases. Previously, we extensively demonstrated the usability of mild electrical stimulation (MES) with low frequency pulse current at 55 pulses per second (MES55) for several disease conditions. Here we found that MES with high frequency pulse-current (5500 pulse per second; MES5500) suppressed the overproduction of pro-inflammatory cytokines induced by phorbol myristate acetate/ionomycin in Jurkat T cells and primary splenocytes. MES5500 also suppressed the overproduction of inflammatory cytokines, improved liver damage and reduced mouse spleen enlargement in concanavalin-A-treated BALB/c mice. The molecular mechanism underlying these effects included the ability of MES5500 to induce modest amount of hydrogen peroxide and control multiple signaling pathways important for immune regulation, such as NF-κB, NFAT and NRF2. In the treatment of various inflammatory and immune-related diseases, suppression of excessive inflammatory cytokines is key, but because immunosuppressive drugs used in the clinical setting have serious side effects, development of safer methods of inhibiting cytokines is required. Our finding provides evidence that physical medicine in the form of MES5500 may be considered as a novel therapeutic tool or as adjunctive therapy for inflammatory and immune-related diseases.


Assuntos
Citocinas/imunologia , Terapia por Estimulação Elétrica/métodos , Peróxido de Hidrogênio/imunologia , Imunossupressão/métodos , Inflamação/imunologia , Inflamação/terapia , Animais , Concanavalina A , Feminino , Humanos , Inflamação/induzido quimicamente , Células Jurkat , Fígado/imunologia , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia , Baço/patologia
14.
Cell Tissue Bank ; 21(3): 405-425, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32588163

RESUMO

Acute respiratory infections as one of the most common problems of healthcare systems also can be considered as an important reason for worldwide morbidity and mortality from infectious diseases. Coronaviruses are a group of well-known respiratory viruses that can cause acute respiratory infections. At the current state, the 2019 novel coronavirus is cited as the most worldwide problematic agent for the respiratory system. According to investigations, people with old age and underlying diseases are at higher risk of 2019 novel coronavirus infection. Indeed, they may show a severe form of the disease (with severe acute respiratory infections). Based on the promising role of cell therapy and regenerative medicine approaches in the treatment of several life-threatening diseases, it seems that applying cell-based approaches can also be a hopeful strategy for improving subjects with severe acute respiratory infections caused by the 2019 novel coronavirus. Herein, due to the amazing effects of mesenchymal stem cells in the treatment of various diseases, this review focuses on the auxiliary role of mesenchymal stem cells to reduce inflammatory processes of acute respiratory infections caused by the 2019 novel coronavirus.


Assuntos
Infecções por Coronavirus/terapia , Inflamação/terapia , Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Regeneração , Infecções por Coronavirus/complicações , Humanos , Inflamação/etiologia , Pandemias , Pneumonia Viral/complicações , Medicina Regenerativa/métodos
15.
PLoS One ; 15(6): e0232493, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32511256

RESUMO

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality and spontaneous PTB is a major contributor. The preceding inflammation/infection contributes not only to spontaneous PTB but is associated with neonatal morbidities including impaired brain development. Therefore, control of exaggerated immune response during pregnancy is an attractive strategy. A potential candidate is synthetic PreImplantation Factor (sPIF) as sPIF prevents inflammatory induced fetal loss and has neuroprotective properties. Here, we tested maternal sPIF prophylaxis in pregnant mice subjected to a lipopolysaccharides (LPS) insult, which results in PTB. Additionally, we evaluated sPIF effects in placental and microglial cell lines. Maternal sPIF application reduced the LPS induced PTB rate significantly. Consequently, sPIF reduced microglial activation (Iba-1 positive cells) and preserved neuronal migration (Cux-2 positive cells) in fetal brains. In fetal brain lysates sPIF decreased IL-6 and INFγ concentrations. In-vitro, sPIF reduced Iba1 and TNFα expression in microglial cells and reduced the expression of pro-apoptotic (Bad and Bax) and inflammatory (IL-6 and NLRP4) genes in placental cell lines. Together, maternal sPIF prophylaxis prevents PTB in part by controlling exaggerated immune response. Given the sPIF`FDA Fast Track approval in non-pregnant subjects, we envision sPIF therapy in pregnancy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/terapia , Peptídeos/farmacologia , Complicações na Gravidez/tratamento farmacológico , Nascimento Prematuro/prevenção & controle , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Encéfalo/imunologia , Linhagem Celular , Modelos Animais de Doenças , Feminino , Inflamação/imunologia , Lipopolissacarídeos , Camundongos , Microglia/efeitos dos fármacos , Microglia/imunologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Gravidez , Complicações na Gravidez/imunologia , Nascimento Prematuro/imunologia
16.
Medicine (Baltimore) ; 99(22): e20468, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481454

RESUMO

RATIONALE: Although prosthetic loosening caused by poor prosthesis positioning is common after total hip arthroplasty (THA), an inflammation caused by poor prosthesis positioning is rare. We report a case in which a THA-related inflammation was indeed caused by poor prosthesis positioning. PATIENT CONCERNS: A 64-year-old woman was admitted to our hospital with a history of persistent hip pain that had started after she had undergone THA 4 years previously. In addition, she complained of swelling of the hip that had begun 2 months ago. DIAGNOSIS: Her pain and swelling was initially thought to be caused by an infection, but was eventually diagnosed as inflammation caused by prosthesis loosening, that was in line with finding that her preoperative and intraoperative cultures showed no bacterial or fungal growth. This case posed many questions and difficulties during the diagnostic and treatment stages. INTERVENTIONS: Routine diagnosis of periprosthetic suspected infection includes blood test, erythrocyte sedimentation rate, C-reactive protein level, bacterial and fungal cultures, and pathology examinations, which were performed. Finally, this case was eventually diagnosed as inflammation, the prosthesis was removed and antibiotics administered. It was replaced 6 months later. OUTCOMES: Except for the erythrocyte sedimentation rate and C-reactive protein levels, X rays, routine blood tests, bacterial and fungal cultures (3 times), and other tests were within the normal range. Positive pathological examinations of synovium during and after the operation indicated chronic inflammation and eliminated inflammation in other areas. Postoperative effect of the second-stage THA was good, with the patient highly satisfied after 6 months. LESSONS: The operative method and position of a joint prosthesis are extremely important. A poorly positioned prosthesis worsens with wear. Wear particles then lead to long-term localized aseptic inflammation with swelling and fever and eventually to low-virulence infection. Prosthetic loosening may be found even at long-term follow-up evaluations after THA in patients with a poorly positioned prosthesis, eventually leading to the need for revision. We had 2 questions: should early revision be considered when a prosthesis had not been properly positioned? In the absence of any confirmation of infection, should a patient suspected of having a periprosthetic infection be treated as early as possible?


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Inflamação/etiologia , Falha de Prótese , Diagnóstico Diferencial , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/patologia , Inflamação/terapia , Pessoa de Meia-Idade
17.
Nutrients ; 12(5)2020 May 19.
Artigo em Inglês | MEDLINE | ID: covidwho-344364

RESUMO

The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has engulfed the world, affecting more than 180 countries. As a result, there has been considerable economic distress globally and a significant loss of life. Sadly, the vulnerable and immunocompromised in our societies seem to be more susceptible to severe COVID-19 complications. Global public health bodies and governments have ignited strategies and issued advisories on various handwashing and hygiene guidelines, social distancing strategies, and, in the most extreme cases, some countries have adopted "stay in place" or lockdown protocols to prevent COVID-19 spread. Notably, there are several significant risk factors for severe COVID-19 infection. These include the presence of poor nutritional status and pre-existing noncommunicable diseases (NCDs) such as diabetes mellitus, chronic lung diseases, cardiovascular diseases (CVD), obesity, and various other diseases that render the patient immunocompromised. These diseases are characterized by systemic inflammation, which may be a common feature of these NCDs, affecting patient outcomes against COVID-19. In this review, we discuss some of the anti-inflammatory therapies that are currently under investigation intended to dampen the cytokine storm of severe COVID-19 infections. Furthermore, nutritional status and the role of diet and lifestyle is considered, as it is known to affect patient outcomes in other severe infections and may play a role in COVID-19 infection. This review speculates the importance of nutrition as a mitigation strategy to support immune function amid the COVID-19 pandemic, identifying food groups and key nutrients of importance that may affect the outcomes of respiratory infections.


Assuntos
Anti-Inflamatórios/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/terapia , Inflamação/terapia , Terapia Nutricional/métodos , Estado Nutricional , Pneumonia Viral/terapia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citocinas/sangue , Dieta/métodos , Humanos , Inflamação/imunologia , Estado Nutricional/imunologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/virologia
19.
J Exp Med ; 217(6)2020 06 01.
Artigo em Inglês | MEDLINE | ID: covidwho-156716

RESUMO

The novel 2019 strain of coronavirus is a source of profound morbidity and mortality worldwide. Compared with recent viral outbreaks, COVID-19 infection has a relatively high mortality rate, the reasons for which are not entirely clear. Furthermore, treatment options for COVID-19 infection are currently limited. In this Perspective, we explore the contributions of the innate and adaptive immune systems to both viral control as well as toxicity during COVID-19 infections and offer suggestions to both understand and therapeutically modulate anti-COVID immunity.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Imunidade Adaptativa/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/terapia , Humanos , Hipóxia/patologia , Hipóxia/terapia , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Inflamação/terapia , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Linfopenia/imunologia , Linfopenia/patologia , Linfopenia/terapia , Macrófagos/imunologia , Macrófagos/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/terapia , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/patologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade
20.
Int J Mol Sci ; 21(9)2020 May 10.
Artigo em Inglês | MEDLINE | ID: covidwho-209969

RESUMO

The current pandemic coronavirus, SARS-CoV-2, is a global health emergency because of its highly contagious nature, the great number of patients requiring intensive care therapy, and the high fatality rate. In the absence of specific antiviral drugs, passive prophylaxis, or a vaccine, the treatment aim in these patients is to prevent the potent virus-induced inflammatory stimuli from leading to the acute respiratory distress syndrome (ARDS), which has a severe prognosis. Here, the mechanism of action and the rationale for employing immunological strategies, which range from traditional chemically synthesized drugs, anti-cytokine antibodies, human immunoglobulin for intravenous use, to vaccines, are reviewed.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Imunoterapia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/terapia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/terapia , Pandemias , Pneumonia Viral/patologia
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