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BACKGROUND: The US Food and Drug Administration (FDA) issued a warning in December 2018 regarding an increased risk of aortic aneurysms and aortic dissections associated with fluoroquinolone (FQ) use. This warning specifically targeted older adults and patients with conditions such as hypertension, Marfan syndrome, Ehlers-Danlos syndrome, atherosclerosis, peripheral vascular disease and history of aneurysms. OBJECTIVE: To evaluate the impact of the safety warning on prescribing trends of FQs in the targeted population. METHODS: This cross-sectional study with an interrupted time series (ITS) analysis (January 2018-December 2019) used a 25% random sample of IQVIA PharMetrics® Plus for Academics health plan claims database. The impact of the warning on FQ utilisation was quantified among the targeted population and a non-targeted population. RESULTS: From 2018 to 2019, both study populations saw a decrease in the year-over-year percent change of FQ prescriptions per 100 000 beneficiaries (-11%, from 14 227 to 12 662, targeted; -15%, from 5227 to 4446, non-targeted) and proportion of FQ use versus other antibiotics (from 15.6% to 13.8%, targeted; from 9.4% to 8%, non-targeted). In the targeted population, the ITS analysis did not show a significant trend change, a change in level or postwarning trend in the monthly rate of FQ prescriptions per 1000 beneficiaries. A positive trend change was observed in the non-targeted population (0.07, <0.01-0.13), but there were no significant changes in level or post-warning trend. CONCLUSION: We did not find a change in FQ prescription rates after the warning. The utility of safety advisories as a primary tool for mitigating FQ use in high-risk populations should be revisited.
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Antibacterianos , Aneurisma de la Aorta , Disección Aórtica , Fluoroquinolonas , United States Food and Drug Administration , Humanos , Estados Unidos/epidemiología , Estudios Transversales , Disección Aórtica/epidemiología , United States Food and Drug Administration/estadística & datos numéricos , Aneurisma de la Aorta/epidemiología , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/uso terapéutico , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Análisis de Series de Tiempo Interrumpido , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Pautas de la Práctica en Medicina/normas , Prescripciones de Medicamentos/estadística & datos numéricos , AdultoRESUMEN
BACKGROUND: Opioid overdose deaths in the United States remain a major public health crisis. Little is known about counties with high rates of opioid overdose mortality but low availability of opioid use disorder (OUD) treatment facilities. We sought to identify characteristics of United States (US) counties with high rates of opioid overdose mortality and low rates of opioid treatment facilities. METHODS: Rates of overdose mortality from 3,130 US counties were compared with availability of opioid treatment facilities that prescribed or allowed medications for OUD (MOUD), from 2018-2019. The outcome variable, "risk-availability mismatch" county, was a binary indicator of a high rate (above national average) of opioid overdose mortality with a low (below national average) rate of opioid treatment facilities. Covariates of interest included county-level sociodemographics and rates of insurance, unemployment, educational attainment, poverty, urbanicity, opioid prescribing, depression, heart disease, Gini index, and Theil index. Multilevel logistic regression, accounting for the clustering of counties within states, was used to determine associations with being a "risk-availability mismatch" county. RESULTS: Of 3,130 counties, 1,203 (38.4%) had high rates of opioid overdose mortality. A total of 1,098 counties (35.1%) lacked a publicly-available opioid treatment facility in 2019. In the adjusted model, counties with an additional 1% of: white residents (odds ratio, OR, 1.02; 95% CI, 1.01-1.03), unemployment (OR, 1.11; 95% CI, 1.05-1.19), and residents without insurance (OR, 1.04; 95% CI, 1.01-1.08) had increased odds of being a mismatch county. Counties that were metropolitan (versus non-metropolitan) had an increased odds of being a mismatch county (OR, 1.85; 95% CI, 1.45-2.38). CONCLUSION: Assessing mismatch between treatment availability and need provides useful information to characterize counties that require greater public health investment. Interventions to reduce overdose mortality are unlikely to be effective if they do not take into account diverse upstream factors, including sociodemographics, disease burden, and geographic context of communities.
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Sobredosis de Droga , Sobredosis de Opiáceos , Trastornos Relacionados con Opioides , Humanos , Estados Unidos/epidemiología , Analgésicos Opioides/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Sobredosis de Opiáceos/tratamiento farmacológico , Pautas de la Práctica en Medicina , Sobredosis de Droga/tratamiento farmacológicoRESUMEN
Monkeypox is an infectious and contagious zoonotic disease caused by the Orthopoxvirus species and was first identified in Africa. Recently, this infectious disease has spread widely in many parts of the world. Fever, fatigue, headache, and rash are common symptoms of monkeypox. The presence of lymphadenopathy is another prominent and key symptom of monkeypox, which distinguishes this disease from other diseases and is useful for diagnosing the disease. This disease is transmitted to humans through contact with or eating infected animals as well as objects infected with the virus. One of the ways to diagnose this disease is through PCR testing of lesions and secretions. To prevent the disease, vaccines such as JYNNEOS and ACAM2000 are available, but they are not accessible to all people in the world, and their effectiveness and safety need further investigation. However, preventive measures such as avoiding contact with people infected with the virus and using appropriate personal protective equipment are mandatory. The disease therapy is based on medicines such as brincidofovir, cidofovir, and Vaccinia Immune Globulin Intravenous. The injectable format of tecovirimat was approved recently, in May 2022. Considering the importance of clinical care in this disease, awareness about the side effects of medicines, nutrition, care for conjunctivitis, skin rash, washing and bathing at home, and so on can be useful in controlling and managing the disease.
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Exantema , Mpox , Humanos , Animales , Administración Intravenosa , África , Benzamidas , CidofovirRESUMEN
Early-life cues shape the immune system during adulthood. However, early-life signaling pathways and their temporal functions are not well understood. Herein, we demonstrate that the cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2), which are E3 ubiquitin ligases, sustain interleukin (IL)-17-producing γ δ T cells (γδT17) and group 3 innate lymphoid cells (ILC3) during late neonatal and prepubescent life. We show that cell-intrinsic deficiency of cIAP1/2 at 3-4 wk of life leads to downregulation of the transcription factors cMAF and RORγt and failure to enter the cell cycle, followed by progressive loss of γδT17 cells and ILC3 during aging. Mice deficient in cIAP1/2 have severely reduced γδT17 cells and ILC3, present with suboptimal γδT17 responses in the skin, lack intestinal isolated lymphoid follicles, and cannot control intestinal bacterial infection. Mechanistically, these effects appear to be dependent on overt activation of the non-canonical NF-κB pathway. Our data identify cIAP1/2 as early-life molecular switches that establish effective type 3 immunity during aging.
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Inmunidad Innata , Ubiquitina , Ratones , Animales , Linfocitos , Interleucinas/metabolismo , EnvejecimientoRESUMEN
INTRODUCTION: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. METHODS: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. RESULTS: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR <60 mL/min/1.73 m2), as well as 28% of patients with albuminuria (≥30 mg/g). The median (IQR) of serum TG was 148 (100, 222) mg/dL. We observed a slight positive linear association between TG and incident CKD after adjustment for Case-Mix and Laboratory variables among non-albuminuric and microalbuminuric patients. The relationship of high TG trended towards a higher risk of ESRD in CKD 3A non-albuminuric patients and in CKD 3A and 4/5 patients with microalbuminuria. CONCLUSION: In a large cohort, we have shown that elevated TGs are associated with all kidney outcomes tested independently of other metabolic syndrome components in diabetic patients with normal eGFR and normal albumin excretion rate, but the association is weaker in some groups of diabetic patients with preexisting renal complications.
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Diabetes Mellitus , Fallo Renal Crónico , Síndrome Metabólico , Insuficiencia Renal Crónica , Veteranos , Femenino , Humanos , Persona de Mediana Edad , Anciano , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Estudios Retrospectivos , Albuminuria/epidemiología , Albuminuria/etiología , Triglicéridos , Riñón , Diabetes Mellitus/epidemiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Tasa de Filtración Glomerular , Factores de RiesgoRESUMEN
Accelerating Food and Drug Administration (FDA) product approval to market based on surrogate markers in the absence of proven efficacy creates a risk of adverse outcomes for affected patients, even in response to a life-threatening condition, such as in this case, Alzheimer's disease. FDA's recent unexpected approval of aducanumab, despite the unified opposition of its own highly respected advisory committee after the early termination of two efficacy trials, creates the potential risk of adverse effects and lack of clinical efficacy at very high costs. In view of these concerns, a thorough review of the issues and pressures that led to this decision is worth the careful consideration of the clinical and scientific communities with regard to whether this approval represents a calculated and balanced compassionate decision versus a disturbing precedent.
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Anticuerpos Monoclonales Humanizados , Aprobación de Drogas , Humanos , Biomarcadores , United States Food and Drug Administration , Terminación Anticipada de los Ensayos Clínicos , Comités ConsultivosRESUMEN
A hypercoagulable state associated with coronavirus disease 2019 (COVID-19) has been well documented and is believed to be strongly supported by a proinflammatory state. The hypercoagulable state in turn results in increased incidence of arterial and venous thromboembolism (VTE) seen in hospitalized COVID-19 when compared with hospitalized non-COVID-19 patient cohorts. Moreover, patients with arterial or VTE and COVID-19 have higher mortality compared with COVID-19 patients without arterial or VTE. Prevention of arterial or VTE thus remains an essential question in the management of COVID-19 patients, especially because of high rates of reported microvascular and macrovascular thrombosis. This has prompted multiple randomized control trials (RCTs) evaluating different anticoagulation strategies in COVID-19 patients at various stages of the disease. Herein, we review findings from RCTs in the past 2 years of antithrombotic therapy in critically ill hospitalized patients, noncritically ill hospitalized patients, patients postdischarge from the hospital, and outpatients. RCTs in critically ill patients demonstrated therapeutic dose anticoagulation does not improve outcomes and has more bleeding than prophylaxis dose anticoagulant in these patients. Trials in noncritically ill hospitalized patients showed a therapeutic dose anticoagulation with a heparin formulation might improve clinical outcomes. Anticoagulation with a direct oral anticoagulant posthospital discharge may improve outcomes, although there is a large RCT in progress. Nonhospitalized COVID-19 patients have an insufficient burden of events to be candidates for antithrombotic therapy. Anticoagulation in pregnant and lactating patients with COVID-19, as well as antiplatelet therapy for COVID-19, is also reviewed.
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COVID-19 , Tromboembolia Venosa , Humanos , COVID-19/complicaciones , Tromboembolia Venosa/etiología , Fibrinolíticos/uso terapéutico , Enfermedad Crítica , Anticoagulantes/efectos adversosRESUMEN
OBJECTIVES: Serum creatinine-based estimated glomerular filtration rate equations and muscle mass are powerful markers of health and mortality risk. However, the serum creatinine-to-cystatin-C ratio may be a better indicator of health status. The objective of this study was to describe the relationship between creatinine-to-cystatin-C ratio and all-cause mortality when stratifying patients as per race and as per chronic kidney disease status. METHODS: This was a retrospective cohort study examining black and nonblack US veterans between October 2004 and September 2019, with baseline cystatin C and creatinine data from those not on dialysis during the study period. Veterans were divided into four creatinine-to-cystatin-C ratio groups: <0.75, 0.75-<1.00, 1.0-<1.25, and ≥1.25. The primary outcome of interest was all-cause mortality subsequent to the cystatin C laboratory measure. RESULTS: Among 22,316 US veterans, the mean (± standard deviation) age of the cohort was 67 ± 14 years, 5% were female, 82% were nonblack, and 18% were black. The proportion of black veterans increased across creatinine-to-cystatin-C ratio groups. In the fully adjusted model, compared with the reference (creatinine-to-cystatin-C ratio: 1.00-<1.25), a creatinine-to-cystatin-C ratio <0.75 had the highest mortality risk among both black and nonblack veterans (nonblack: hazard ratio [HR] [95% confidence interval {CI}]: 3.01 [2.78-3.26] and black: 4.17 [3.31-5.24]). A creatinine-to-cystatin-ratio ≥1.25 was associated with lower death risk than the referent in both groups (nonblack: HR [95% CI]: 0.89 [0.80-0.99] and black: HR [95% CI]: 0.55 [0.45-0.69]). However, there was a significant difference in the effect by race (Wald's P-value: <0.01). CONCLUSIONS: Higher creatinine-to-cystatin-C ratios indicate better health status and are strongly associated with lower mortality risk regardless of the kidney function level, and the relation was similar for both black and nonblack veterans, but with different strengths of effect across racial groups. Thereby, use of a fixed race coefficient in estimating kidney function may be biased.
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Cistatina C , Insuficiencia Renal Crónica , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Creatinina , Estudios Retrospectivos , Factores Raciales , Biomarcadores , Tasa de Filtración Glomerular/fisiología , Insuficiencia Renal Crónica/complicaciones , MúsculosRESUMEN
INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected certain high-risk populations, including those with underlying chronic illnesses and those who are socioeconomically disadvantaged. METHODS: Our study evaluated county-level rates of fully vaccinated populations after classifying counties based on rates of non-communicable diseases (NCDs) and socioeconomic inequities below the 25th percentile of overall distribution of counties for each measure as low, counties above the 75th percentile as high, and all other counties as medium. RESULTS: Counties with higher rates of non-communicable diseases and socioeconomic disparities had lower COVID-19 vaccination coverage than did counties with lower rates of non-communicable diseases and socioeconomic disparities. Co-occurrence of high NCD and high socioeconomic vulnerability among counties in the lower half of vaccination coverage was also found for some counties. CONCLUSION: These findings demonstrate the co-occurrence of low rates of vaccine coverage, high rates of NCDs, and high rates of socioeconomic disparities as a syndemic.
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COVID-19 , Enfermedades no Transmisibles , Vacunas , Humanos , Estados Unidos , Enfermedades no Transmisibles/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Sindémico , Vacunas contra la COVID-19 , Vacunación , Factores SocioeconómicosRESUMEN
PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mostly uses the angiotensin-converting enzyme 2 (ACE-2) as cellular receptor for entering the host cells. Some, but not all, animal studies have shown that renin-angiotensin-aldosterone system (RAAS) inhibitors can increase ACE-2 expression. On that premise, it was hypothesized that these agents could make it more likely to develop coronavirus disease 2019 (COVID-19). On the other hand, there was also evidence that being on these agents could lessen the severity of the lung injury in patients with severe SARS-CoV-2 infection. Herein, we review the available evidence on the role of RAAS inhibitors on SARS-CoV-2 and COVID-19 development. RECENT FINDINGS: Recent randomized controlled trials demonstrate that RAAS blockade or withdrawal does not influence the severity of COVID-19 in patients who are already on these medications. Currently, there is no evidence to support stopping RAAS inhibitors in patients hospitalized for COVID-19. Several questions still need to be addressed. Ongoing studies are currently evaluating the de novo use of RAAS inhibitors in patients with COVID-19. Another area that needs to be investigated is whether or not using these medications increase the risk of infection. SUMMARY: The wealth of evidence indicates that ACE inhibitors and angiotensin-receptor blocker administration has no harmful effects on hospitalizations and severity of COVID-19 in patients already on these medications and might even reduce mortality among hypertensive patients diagnosed with COVID-19. More evidence and data need to be collected, and at this time, these agents should not be discontinued.
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Tratamiento Farmacológico de COVID-19 , Hipertensión , Antagonistas de Receptores de Angiotensina/uso terapéutico , Animales , Humanos , Hipertensión/tratamiento farmacológico , Sistema Renina-Angiotensina , SARS-CoV-2RESUMEN
Human monkeypox is a zoonotic orthopoxvirus with presentation similar to smallpox. Monkeypox is transmitted incidentally to humans when they encounter infected animals. Reports have shown that the virus can also be transmitted through direct contact (sexual or skin-to-skin), respiratory droplets, and via fomites such as towels and bedding. Multiple medical countermeasures are stockpiled for orthopoxviruses such as monkeypox. Two vaccines are currently available, JYNNEOSTM (live, replication incompetent vaccinia virus) and ACAM2000® (live, replication competent vaccinia virus). While most cases of monkeypox will have mild and self-limited disease, with supportive care being typically sufficient, antivirals (e.g. tecovirimat, brincidofovir, cidofovir) and vaccinia immune globulin intravenous (VIGIV) are available as treatments. Antivirals can be considered in severe disease, immunocompromised patients, pediatrics, pregnant and breastfeeding women, complicated lesions, and when lesions appear near the mouth, eyes, and genitals. The purpose of this short review is to describe each of these countermeasures.
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Mpox , Viruela , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , Niño , Cidofovir , Femenino , Humanos , Mpox/tratamiento farmacológico , Mpox/prevención & control , Embarazo , Viruela/tratamiento farmacológico , Virus VacciniaRESUMEN
INTRODUCTION: In COVID-19 pneumonia, there is a massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB2 â« PGE2 > PGD2 in the lungs, and 11-dehydro-TxB2, a TxA2 metabolite, in the systemic circulation. While TxA2 stimulates thromboxane prostanoid (TP) receptors, 11-dehydro-TxB2 is a full agonist of DP2 (formerly known as the CRTh2) receptors for PGD2. Anecdotal experience of using ramatroban, a dual receptor antagonist of the TxA2/TP and PGD2/DP2 receptors, demonstrated rapid symptomatic relief from acute respiratory distress and hypoxemia while avoiding hospitalization. AREAS COVERED: Evidence supporting the role of TxA2/TP receptors and PGD2/DP2 receptors in causing rapidly progressive lung injury associated with hypoxemia, a maladaptive immune response and thromboinflammation is discussed. An innovative perspective on the dual antagonism of TxA2/TP and PGD2/DP2 receptor signaling as a therapeutic approach in COVID-19 is presented. This paper examines ramatroban an anti-platelet, immunomodulator, and antifibrotic agent for acute and long-haul COVID-19. EXPERT OPINION: Ramatroban, a dual blocker of TP and DP2 receptors, has demonstrated efficacy in animal models of respiratory dysfunction, atherosclerosis, thrombosis, and sepsis, as well as preliminary evidence for rapid relief from dyspnea and hypoxemia in COVID-19 pneumonia. Ramatroban merits investigation as a promising antithrombotic and immunomodulatory agent for chemoprophylaxis and treatment.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Carbazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Trombosis , Animales , COVID-19/complicaciones , Quimioprevención , Humanos , Inflamación/tratamiento farmacológico , SARS-CoV-2 , Trombosis/tratamiento farmacológico , Síndrome Post Agudo de COVID-19RESUMEN
Coronavirus disease 2019 (COVID-19) is an infectious respiratory condition sustained by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which manifests prevalently as mild to moderate respiratory tract infection. Nevertheless, in a number of cases the clinical course may deteriorate, with onset of end organ injury, systemic dysfunction, thrombosis and ischemia. Given the clinical picture, baseline assessment and serial monitoring of blood lactate concentration may be conceivably useful in COVID-19. We hence performed a systematic literature review to explore the possible association between increased blood lactate levels, disease severity and mortality in COVID-19 patients, including comparison of lactate values between COVID-19 and non-COVID-19 patients. We carried out an electronic search in Medline and Scopus, using the keywords "COVID-19" OR "SARS-CoV-2" AND "lactate" OR "lactic acid" OR "hyperlactatemia", between 2019 and present time (i.e. October 10, 2021), which allowed to identify 19 studies, totalling 6,459 patients. Overall, we found that COVID-19 patients with worse outcome tend to display higher lactate values than those with better outcome, although most COVID-19 patients in the studies included in our analysis did not have sustained baseline hyperlactatemia. Substantially elevated lactate values were neither consistently present in all COVID-19 patients who developed unfavourable clinical outcomes. These findings suggest that blood lactate monitoring upon admission and throughout hospitalization may be useful for early identification of higher risk of unfavourable COVID-19 illness progression, though therapeutic decisions based on using conventional hyperlactatemia cut-off values (i.e., 2.0 mmol/L) upon first evaluation may be inappropriate in patients with SARS-CoV-2 infection.
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COVID-19 , Hiperlactatemia , Ácido Láctico/sangre , COVID-19/sangre , Hospitalización , Humanos , Hiperlactatemia/virología , SARS-CoV-2RESUMEN
OBJECTIVE: To determine the association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) use and coronavirus disease 2019 (COVID-19) severity and outcomes in US veterans. PATIENTS AND METHODS: We retrospectively examined 27,556 adult US veterans who tested positive for COVID-19 between March to November 2020. Logistic regression and Cox proportional hazards models using propensity score (PS) for weight, adjustment, and matching were used to examine the odds of an event within 60 days following a COVID-19-positive case date and time to death, respectively, according to ACEI and/or ARB prescription within 6 months prior to the COVID-19-positive case date. RESULTS: The overlap PS weighted logistic regression model showed lower odds of an intensive care unit (ICU) admission (odds ratio [OR] 95% CI 0.77, 0.61-0.98) and death within 60 days (0.87, 0.79-0.97) with an ACEI or ARB prescription. Veterans with an ARB-only prescription also had lower odds of an ICU admission (0.64, 0.44-0.92). The overlap PS weighted model similarly showed a lower risk of time to all-cause mortality in veterans with an ACEI or ARB prescription (HR [95% CI]: 0.87, 0.79-0.97) and an ARB only prescription (0.78, 0.67-0.91). Veterans with an ACEI prescription had higher odds of experiencing a septic event within 60 days after the COVID-19-positive case date (1.22, 1.02-1.46). CONCLUSION: In this study of a national cohort of US veterans, we found that the use of an ACEI/ARB in patients with COVID-19 was not associated with increased mortality and other worse outcomes. Future studies should examine underlying pathways and further confirm the relationship of ACEI prescription with sepsis.
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Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , COVID-19/epidemiología , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , COVID-19/mortalidad , Femenino , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , SARS-CoV-2 , Sepsis/epidemiología , Factores Sociodemográficos , VeteranosRESUMEN
Interleukin (IL)-17-producing gamma delta (γδ) T (γδT17) cells are an essential part of innate type 3 immunity against numerous pathogens. At the same time, a large body of evidence from mouse models and human clinical studies suggests that γδT17 cells contribute to the pathogenesis of many inflammatory diseases as well as cancer. It is therefore relevant to elucidate their immunobiology in detail and identify molecules and pathways that can regulate their function. Herein, we investigated the importance of the type I interferon (IFN) signaling system in γδT17 homeostasis and activation. We found that the IFN alpha receptor 1 (IFNAR1) was critical to maintain their normal homeostasis and to promote their activation during cutaneous inflammation. However, this did not require γδT17-intrinsic expression of IFNAR1. In contrast, expression of IFNAR1 by γδT17 cells was required in order to suppress IL-17 production during viral infection. Our data delineate direct from indirect IFNAR1 signaling and reveal an important immunoregulatory role for both tonic and inducible type I IFN in γδT17 cells.