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Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton’s syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17- producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

We present here an evidence-based review of the utility, timing, and indications for laboratory test use in the domains of inflammation, cardiology, hematology, nephrology and co-infection for clinicians managing the care of hospitalized COVID-19 patients. Levels of IL-6, CRP, absolute lymphocyte count, neutrophils and neutrophil-to-lymphocyte ratio obtained upon admission may help predict the severity of COVID-19. Elevated lactate dehydrogenase, ferritin, aspartate aminotransferase, and ᴅ-dimer are associated with severe illness and mortality. Elevated cardiac troponin at hospital admission can alert clinicians to patients at risk for cardiac complications. Elevated proBNP may help distinguish a cardiac complication from noncardiac etiologies. Evaluation for co-infection is typically unnecessary in nonsevere cases but is essential in severe COVID-19, intensive care unit patients, and immunocompromised patients. Doctors managing the complex care of individuals with COVID-19 need timely evidence to guide which lab tests to send to predict outcomes and prevent and treat COVID-19 complications involving the heart, blood clots, the kidney, and other infections that occur during the hospital course. Several lab tests such as IL-6, CRP and white blood cell subset counts may help predict the severity of COVID-19 during the patient's hospital course if obtained when the patient first presents to the hospital. Other tests such as lactate dehydrogenase, ferritin and aspartate aminotransferase are also associated with severe illness and mortality but have less evidence for their utility beyond IL-6, CRP and other tests. A test related to blood coagulation, ᴅ-dimer, is also associated with COVID-19 severity, and it may be used if the patient is suspected of having a blood clot. Two heart biomarkers – cardiac troponin and proBNP – may help doctors diagnose and manage heart-related complications of COVID-19. Patients in the hospital with COVID-19 may be susceptible to other infections, but testing for these is most useful in patients with severe disease, such as those in the intensive care unit. Specific recommendations for testing for viral, bacterial and fungal infections are presented here. The judicious use of laboratory testing can help identify patients at high risk for severe or critical COVID-19 and aid in prevention, diagnosis and treatment of common COVID-19 complications. [ABSTRACT FROM AUTHOR]

A 19‐year‐old woman with no previous cardiac history was admitted to the hospital with third‐degree atrioventricular block and left ventricular dysfunction. Her condition quickly deteriorated to severe biventricular failure and cardiogenic shock requiring mechanical circulatory support. An endomyocardial biopsy revealed lymphocytic myocarditis with no PCR‐detectable viral genomes, with CD8 T‐cell predominance and pro‐inflammatory macrophage expansion shown by myocardial flow cytometry. The therapy consisted of immunosuppression (high‐dose methylprednisolone) and temporary mechanical circulatory support with enhanced ability to achieve left ventricular unloading by combination of extracorporeal membrane oxygenation with Impella (ECMELLA). After 2 weeks of support, complete and sustained recovery from myocarditis was observed. [ABSTRACT FROM AUTHOR]

The calcium-binding protein S100b is secreted by glial cells in the brain and is also expressed by melanocytes. In nanomolar concentrations, S100b is considered to be a neurotrophic factor, but in micromolar concentrations, it is thought to reflect CNS injury and inflammation. Seen as a potential biomarker in traumatic brain injury, meta-analytic data from several studies report that S100b levels are significantly higher in persons with long standing schizophrenia, but also among first-episode patients compared to healthy control subjects. However, ethnic or racial differences are typically not mentioned when reporting levels of S100b. We assessed serum S100b levels in persons with schizophrenia (n = 136) who were participants in two independent research studies using the same enzyme-linked immunoassay (ELISA). African-American subjects had significantly higher levels of S100b (41.9 pg/ml ± 62.2) than Caucasian subjects (24.9 pg/ml ± 45.4) in the combined dataset (Mann-Whitney U = 1307, p < 0.001), as well as in each independent study. There were no significant differences in S100b levels between men and women. No significant correlations were observed between S100b levels and demographic or clinical variables. These data suggest that ethnicity or race should be given serious consideration when studying and interpreting S100b levels in persons with schizophrenia. [ABSTRACT FROM AUTHOR]

Schizophrenia is a complex mental illness characterized by positive and negative symptoms. Antipsychotic medications are the main treatment for this condition; however, many patients have only a partial response. All currently available antipsychotics involve modulation of the dopamine system, although the underlying pathophysiology of this illness remains poorly understood. Increasing evidence suggests that inflammation plays a significant role in the development of schizophrenia. Thus, a medication that modulates both dopamine signaling and inflammation may be a promising treatment for schizophrenia. L-tetrahydropalmatine (l-THP) has modest affinity for dopamine receptors, acting as an antagonist at D1, D2, and D3 receptors. L-THP also has anti-inflammatory effects, decreasing levels of tumor necrosis factor-α and interleukin 6. We performed a 4-week, randomized, double-blind, placebo-controlled trial of oral l-THP (30 mg twice daily) as an adjunctive treatment in 63 adults with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) on stable antipsychotic medication. The primary psychiatric outcome measures were the presence of positive and negative symptoms. Plasma concentrations of 11 cytokines and C-reactive protein (CRP) were also measured. L-THP had no significant effect on any psychiatric measure but was well tolerated and associated with a significant decrease in extrapyramidal symptoms. L-THP significantly increased plasma concentrations, compared with placebo, of two inflammatory markers: soluble intracellular adhesion molecule 1 and CRP. These findings do not support the efficacy of L-THP as an add-on treatment for schizophrenia but suggest that L-THP may have previously unrecognized proinflammatory effects in people with this disease. [ABSTRACT FROM AUTHOR]

Inflammation may play a role in schizophrenia; however, subgroups with immune regulation dysfunction may serve as distinct illness phenotypes with potential different treatment and prevention strategies. Emerging data show that about 30% of people with schizophrenia have elevated antigliadin antibodies of the IgG type, representing a possible subgroup of schizophrenia patients with immune involvement. Also, recent data have shown a high correlation of IgG-mediated antibodies between the periphery and cerebral spinal fluid in schizophrenia but not healthy controls, particularly AGA IgG suggesting that these antibodies may be crossing the blood–brain barrier with resulting neuroinflammation. Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique that allows the quantification of certain neurochemicals in vivo that may proxy inflammation in the brain such as myoinositol and choline-containing compounds (glycerophosphorylcholine and phosphorylcholine). The objective of this exploratory study was to examine the relationship between serum AGA IgG levels and MRS neurochemical levels. We hypothesized that higher AGA IgG levels would be associated with higher levels of myoinositol and choline-containing compounds (glycerophosphorylcholine plus phosphorylcholine; GPC + PC) in the anterior cingulate cortex. Thirty-three participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder had blood drawn and underwent neuroimaging using MRS within 9 months. We found that 10/33 (30%) had positive AGA IgG (≥20 U) similar to previous findings. While there were no significant differences in myoinositol and GPC + PC levels between patients with and without AGA IgG positivity, there were significant relationships between both myoinositol (r = 0.475, p = 0.007) and GPC + PC (r = 0.36, p = 0.045) with AGA IgG levels. This study shows a possible connection of AGA IgG antibodies to putative brain inflammation as measured by MRS in schizophrenia. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DC) is an independent phenotype of diabetic cardiovascular disease. The understanding of the pathogenesis of DC in young patients with type 1 diabetes (T1D) is limited. The cardiac insults of diabetic ketoacidosis (DKA) and progression of DC could include development of antibodies (Abs) to cardiac self-antigens (SAgs) such as: myosin (M), vimentin (V) and k-alpha 1 tubulin (Kα1T). The goal of this study is to determine if the insults of severe DKA and its inflammatory cascade are associated with immune responses to SAgs. Development of Abs to the SAgs were determined by an ELISA using sera collected at three time points in relation to severe DKA (pH < 7.2). Results demonstrate significant differences between the development of Abs to VIM and a previously reported diastolic abnormality (DA) during DKA and its treatment and a NDA group at 2–3 months post DKA (p = 0.0452). A significant association is present between T1D duration (<3 years) and Abs to Kα1T (p = 0.0134). Further, Abs to MYO and VIM are associated with inflammatory cytokines. We propose that severe DKA initiates the synthesis of Abs to cardiac SAgs that are involved in the early immunopathogenesis of DC in young patients with T1D. [ABSTRACT FROM AUTHOR]

Background: Transcriptomic studies hold great potential towards understanding the human aging process. Previous transcriptomic studies have identified many genes with age-associated expression levels; however, small samples sizes and mixed cell types often make these results difficult to interpret. Results: Using transcriptomic profiles in CD14+ monocytes from 1,264 participants of the Multi-Ethnic Study of Atherosclerosis (aged 55-94 years), we identified 2,704 genes differentially expressed with chronological age (false discovery rate, FDR ⩽ 0.001). We further identified six networks of co-expressed genes that included prominent genes from three pathways: protein synthesis (particularly mitochondrial ribosomal genes), oxidative phosphorylation, and autophagy, with expression patterns suggesting these pathways decline with age. Expression of several chromatin remodeler and transcriptional modifier genes strongly correlated with expression of oxidative phosphorylation and ribosomal protein synthesis genes. 17% of genes with age-associated expression harbored CpG sites whose degree of methylation significantly mediated the relationship between age and gene expression (p < 0.05). Lastly, 15 genes with age-associated expression were also associated (FDR ⩽ 0.01) with pulse pressure independent of chronological age. Comparing transcriptomic profiles of CD14+ monocytes to CD4+ T cells from a subset (n = 423) of the population, we identified 30 age-associated (FDR < 0.01) genes in common, while larger sets of differentially expressed genes were unique to either T cells (188 genes) or monocytes (383 genes). At the pathway level, a decline in ribosomal protein synthesis machinery gene expression with age was detectable in both cell types. Conclusions: An overall decline in expression of ribosomal protein synthesis genes with age was detected in CD14+ monocytes and CD4+ T cells, demonstrating that some patterns of aging are likely shared between different cell types. Our findings also support cell-specific effects of age on gene expression, illustrating the importance of using purified cell samples for future transcriptomic studies. Longitudinal work is required to establish the relationship between identified age-associated genes/pathways and aging-related diseases. [ABSTRACT FROM AUTHOR]

Deals with the diagnostic and prognostic value of heart-reactive antibodies circulating in patients with myocarditis or dilated cardiomyopathy. Characteristics of myocarditis or dilated cardiomyopathy; Myosin antibodies; Antibodies to the cardiac beta1-adrenoceptor; Anti-mitochondrial antibodies; Treatment of myocarditis.

IL-13 knockout (KO) BALB/c mice developed severe myosin-induced experimental autoimmune myocarditis (EAM) and coxsackievirus B3 -- induced myocarditis with impaired cardiac function in some of the IL-13 KO mice. Total CD45+ leukocyte, B cell and macrophage were increased in the hearts of IL-13 KO mice. Spleen T cells from IL-13 KO mice were highly activated and had increased proliferation in vitro to myosin. Hearts of IL-13 KO mice had increased levels of the pro, inflammatory and profibrotic cytokines 1L-1b, IL-18, IFN-g, TGF-a, IL-4 and histamine. Severe EAM in IL-13 KO was not due to increased IL-4, as myocarditis was mild in IL-4 KO mice. CD4+CD25+Foxp3+ regulatory T cell numbers were not altered in the heart, but decreased in the spleen of IL-13 KO mice. Thus, IL-13 protects against severe myocarditis in BALB/c mice by inhibiting macrophage, T cells and B cell/antibody-mediated damage to the heart. [ABSTRACT FROM AUTHOR]