1,720,979 research outputs found
Psoriatic uveitis is not an exploded myth
No full textPsoriatic uveitis, a distinct clinical entity quoted for 7% to 25% in psoriatic ophthalmic patients with spondyloarthritis, and for 25.,% +/- 2,3 in meta-analysis of rheumatic patients with a prevalence of HLA-B27 quoted as for 40%-50%, is often misdiagnosed. The model proposed by Conti & Coll. [Clinical Dermatology 2017;5(1):30-36]merits also to drive attention of Dermatologist, Radiologist, General Practitioner to submit those psoriatic patients to an ophthalmological screening
A New Pharmacological Approach Based on Remdesivir Aerosolized Administration on SARS-CoV-2 Pulmonary Inflammation: A Possible and Rational Therapeutic Application
No full textThe new zoonotic coronavirus (SARS-CoV-2) responsible for coronavirus disease (COVID-19) is a new strain of coronavirus not previously seen in humans and which appears to come from bat species. It originated in Wuhan, Hubei Province, China, and spread rapidly throughout the world, causing over 5,569,679 global cases and 351,866 deaths in almost every country in the world, including Europe, particularly Italy. In general, based on existing data published to date, 80.9% of patients infected with the virus develop mild infection; 13.8% severe pneumonia; 4.7% respiratory failure, septic shock or multi-organ failure; 3% of these cases are fatal. Critical patients have been shown to develop acute respiratory distress syndrome (ARDS) and hospitalization in intensive care units. The average age of patients admitted to hospital is 57–79 years, with one third half with an un- derlying disease. Asymptomatic infections have also been described, but their frequency is not known. SARS- CoV-2 transmission is mainly airborne from one person to another via droplets. The data available so far seem to indicate that SARS-CoV-2 is capable of producing an excessive immune reaction in the host. The virus attacks type II pneumocytes in the lower bronchi through the binding of the Spike protein (S protein) to viral receptors, of which the angiotensin 2 conversion enzyme (ACE2) receptor is the most important. ACE2 receptor is widely expressed in numerous tissues, including the oropharynx and conjunctiva, but mostly distributed in ciliated bronchial epithelial cells and type II pneumocytes in the lower bronchi. The arrival of SARS-CoV-2 in the lungs causes severe primary interstitial viral pneumonia that can lead to the “cytokine storm syndrome”, a deadly uncontrolled systemic inflammatory response triggered by the activation of interleukin 6 (IL-6), whose effect is extensive lung tissue damage and disseminated intravascular coagulation (DIC), that are life-threatening for patients with COVID-19. In the absence of a therapy of proven efficacy, current management consists of off-label or compassionate use therapies based on antivirals, antiparasitic agents in both oral and parenteral formulation, anti-inflammatory drugs, oxygen therapy and heparin support and convalescent plasma. Like most respiratory viruses can function and replicate at low temperatures (i.e. 34–35 °C) and assuming viral thermolability of SARS- CoV-2, local instillation or aerosol of antiviral (i.e. remdesivir) in humid heat vaporization (40°–41 °C) in the first phase of infection (phenotype I, before admission), both in asymptomatic but nasopharyngeal swab positive patients, together with antiseptic-antiviral oral gargles and povidone-iodine eye drops for conjunctiva (0,8–5% conjunctival congestion), would attack the virus directly through the receptors to which it binds, significantly decreasing viral replication, risk of evolution to phenotypes IV and V, reducing hospitalization and therefore death
Interleukin-1 family cytokines and mast cells: activation and inhibition.
No full textThis editorial focuses on recent progress reports on mast cells (MCs) and IL-1-family cytokines in the dynamics of inflammation. MCs are cells of haematopoietic derivation that mature and reside in almost all vascularized tissues. MCs are a potential source of cytokines and chemokines which participate in allergic reactions and inflammation. Activated MCs secrete a number of compounds including pro inflammatory cytokines. MCs can be activated by IgE through its receptor FceRI, but also by Toll like receptors. They can be a target for both pro-inflammatory and anti-inflammatory cytokines. 1L-1 activates MCs to release inflammatory chemical mediators, and cytokines/chemokines, an effect which can be potentially inhibited by IL-37. In addition, IL-36 is also a powerfull cytokine with a pro inflammatory activity. IL-38 binds IL-36R and inhibits the pro-inflammatory activity of IL-36, thus performing a therapeutic action. Here, in this article we review the role of MCs in relation to pro inflammatory and anti-inflammatory IL-1 family member cytokines and a possible therapeutic effect in inflammatory disorders
SARS-CoV-2, which induces COVID-19, causes Kawasaki-like disease in children: role of pro-inflammatory and anti-inflammatory cytokines
No full textAcute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic coronavirus disease 2019 (COVID-19). In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis. These clinical signs are mediated by proinflammatory cytokines. In recent studies it has been noted that COVID-19 pandemic can affect patients of all ages, including children (even if less severely) who were initially thought to be immune. Kawasaki disease is an autoimmune acute febrile inflammatory condition, which primarily affects young children. The disease can present immunodeficiency with the inability of the immune system to fight inflammatory pathogens and leads to fever, rash, alterations of the mucous membranes, conjunctiva infection, pharyngeal erythema, adenopathy, and inflammation. In the COVID-19 period, virus infection aggravates the condition of Kawasaki disease, but it has also been noted that children affected by SARS-V-2 may develop a disease similar to Kawasaki’s illness.However, it is uncertain whether the virus alone can give Kawasaki disease-like forms. As in COVID-19, Kawasaki disease and its similar forms are mediated by pro-inflammatory cytokines produced by innate immunity cells such as macrophages and mast cells (MCs). In light of the above, it is therefore pertinent to think that by blocking pro-inflammatory cytokines with new anti-inflammatory cytokines, such as IL-37 and IL-37, it is possible to alleviate the symptoms of the disease and have a new available therapeutic tool. However, since Kawasaki and Kawasaki-like diseases present immunodeficiency, treatment with anti-inflammatory/immunosuppressant molecules must be applied very carefully
Mast cell virus infection and inflammatory cytokines
No full textMast cells (MCs) are hematopoietic cells developed from bone marrow progenitors in response to the ligand stem cell factor, a trans-membrane tyrosine kinase kit receptor. MCs are located virtually in all vascularized tissues and in proximity to neurons and play a decisive role in both innate and adaptive immune responses. Their activation is involved in oxidative stress correlated with infection and inflammation. Pro-inflammatory cytokines are secreted by MCs after physiologic and psychological stress due to virus infection, including SARS-CoV-2. MCs, along with macrophages and pulmonary alveolar epithelial cells, are the main targets attacked by the coronavirus. COVID-19 induced by SARS-CoV-2
causes inflammatory stress which activates MCs to secrete corticotrophin-releasing hormone (CRH), SP, IL-6, TNF, and IL-1. Toll-like receptor (TLR) virus activation in MCs leads to pro-inflammatory cytokine generation without degranulation, an effect that can be inhibited by IL-10, IL-4, IL-1Ra and IL-37.
TLR has the ability to recognize extracellular PAMPs by causing the transcription of NLRP, pro-IL-1, and other pro-inflammatory cytokines. The multi-protein complex, comprising pro-caspase-1, activates caspase-1 which in turn activates pro-IL-1 that is transformed into highly inflammatory mature IL-1.
In COVID-19, viral RNA is specifically recognized by TLR, followed by recruiting the signal transfer proteins MyD88, IRAK, IKK and TRAF6 which can activate the NF-κB, resulting in transcription of the pro-inflammatory cytokines IL-1 and TNF, responsible for the “cytokine storm” phenomenon.
Meanwhile, a new variant of the coronavirus-19 called C.1.2. has been discovered in the United States in the past few days, the effects of which are unknown, and it is therefore of great concern. Researchers are now testing it on immune cells to see if they react and are comparing it to a delta variant. Thus, from
the existing data in biomedical literature, we can conclude that the suppression of pro-inflammatory cytokines in viral infections (including COVID-19) mediated by MCs represents a promising therapy not only in this field of medicine, but also in autoimmune, allergic, and cardiovascular disorders, as well as tumor inflammation where MCs play a key role
Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by COVID-19: anti-inflammatory strategies
No full textCoronavirus-19 (COVI-19) involves humans as well as animals and may cause serious damage to the respiratory tract, including the lung: coronavirus disease (COVID-19). This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease. When COVI-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6. The binding of COVI-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1β which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1β which is a mediator of lung inflammation, fever and fibrosis. Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections. Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18Rα receptor. IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase. This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1β, IL-6, TNF and CCL2. The suppression of IL-1β by IL-37 in inflammatory state induced by coronavirus-19 can have a new therapeutic effect previously unknown. Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages. IL-38 is also a suppressor cytokine which inhibits IL-1β and other pro-inflammatory IL-family members. IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by coronavirus-19, providing a new relevant strategy
CAR-T cell therapy causes inflammation by IL-1 which activates inflammatory cytokine mast cells: anti-inflammatory role of IL-37
No full textChimeric antigen receptor (CAR) T cells are genetically modified T cells that act against cancer. When CAR-T cells are administered they can trigger inflammatory cytokines and increase toxicity. Interleukin (IL)-1 is the classic cytokine that mediates inflammatory reactions including those that occur in CAR-T-cell therapy. IL-1 also induces IL-33 in mast cells (MCs), amplifying the allergic reaction. IL- 37 (ILF7) is an IL-1 family member which binds IL-18 receptor alpha (IL-18Rα) chain and suppresses innate and acquired immunity. IL-37 is an anti-inflammatory cytokine which inhibits pro-inflammatory cytokines including IL-1 and IL-33. Here, we hypothesize that inflammation and toxicity generated in tumor CAR-T therapy could be inhibited by IL-37, contributing to an improvement in the treatment of tumors with CAR-T therapy
New insight into systemic mastocytosis mediated by cytokines IL-1 beta and IL-33: Potential inhibitory effect of IL-37
No full textSystemic mastocytosis in various forms is characterized by mast cell (MC) infiltration of the bone marrow and other internal organs. The most common form is the indolent one with life expectancy similar to the normal population, while the systemic aggressive myeloproliferative type presents serious damage to various organs and is associated with mature and immature atypical mast cells. In systemic mastocytosis patients, MCs could be activated with consequent severe anaphylactic reactions, along with other symptoms. MCs, which are reactive to a variety of external factors such as allergens or other inflammatory or physical stimuli, derive from pluripotent cellular progenitor CD34(+) which leaves the bone marrow as CD34(+)/CD17(+) for implantation in the tissues where they reach maturation. MCs participate in the innate and adaptive immune system where they play a role in host defense. Activation of MCs occurs through the binding of IgE to Fc epsilon RI receptor, and initiates the phosphorylation and activation of the p38 tyrosine MAP kinase. After various reactions there is a subsequent translation and generation of pro-inflammatory cytokines which are strongly linked to allergic inflammation and mastocytosis. Human cytokine interleukin-37 (IL-37), a unique IL-1 beta family member, has strong protective and anti-inflammatory properties, influencing cellular metabolism. We investigated the effect of IL-37 on inflammation in mastocytosis and report that the hematopoietic expression of IL-37 can reduce the inflammatory state in this disease. IL-37 limits excessive inflammation, which suggests that IL-37 may be beneficial to the metabolic and inflammatory process and is a candidate as a potential new therapeutic agent
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