Association of level of IL-6, IL-10, IL-18, tumour necrosis factor-α with rheumatic mitral stenosis and subsequent pulmonary hypertension

Background: Objective of the study was to provide insight on the immune response in patients of rheumatic heart disease, mitral stenosis and evaluation of various cytokines in pulmonary hypertension secondary to rheumatic heart disease.Methods: Total 163 subjects, more than 18 year of age, were enrolled in this study. 84 subjects with rheumatic mitral stenosis (group A) diagnosed on two-dimensional echocardiography (2D echo) and 79 normal healthy volunteers (group B). Patients with mitral stenosis were further divided into subgroups based on severity of mitral stenosis [mitral valve area (MVA >1 cm2 and MVA <1 cm2) (subgroup Aa and Ab)] and presence or absence of pulmonary hypertension [pulmonary arterial systolic pressure (PASP >36 mm Hg) (subgroup Ac and Ad)]. Interleukins IL-6, IL-10, IL-18, tumour necrosis factor alpha (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) levels were assessed in both groups.Results: Mean IL-6, IL-10, IL-18, TNF-α and hs-CRP in group A and group B was 6.57±3.53 and 2.73±1 (p≤0.001), 8.185±2.8 and 3.51±0.86 (p≤0.001), 136.31±89.0 and 47.96±9.76 (p≤0.001), 21.26±18.59 and 5.36±3.57 (p≤0.001), 4.69±6.3 and 2.63±2.22 (p≤0.008) respectively. On subgroup analysis mean TNF-α in subgroup Aa was 20.71±16.84, while in subgroup Ab was 7.56±1.93 (p≤0.001). Mean IL-10 in subgroup Ac and Ad was 8.74±3.29 and 7.47±1.82, respectively. Differences in levels of other cytokines in these subgroups were not found statistically significant.Conclusions: This study finds increased IL-6, IL-10, IL-18, TNF-α and hs-CRP levels in subjects with rheumatic mitral stenosis. Subjects with severe mitral stenosis had increased TNF-α levels. Subjects of mitral stenosis having pulmonary hypertension had increased IL-10 levels.

Impact of treatment with immunomodulators and tumour necrosis factor antagonists on the incidence of infectious events in patients with inflammatory bowel disease

Background: Corticosteroids, immunomodulators (IM) and tumour necrosis factor antagonists (anti-TNF) are commonly used in the treatment of inflammatory bowel disease (IBD) but they also supress the defence against infectious disease. The aim of this study was to analyse the incidence of infectious events in patients with IBD and the association to concomitant medical therapy. Methods: We performed a retrospective medical chart review of patients with IBD aged 18–65 years included in the Swedish Registry of Inflammatory Bowel Disease in the catchment area of Umeå University Hospital, Sweden. Data were collected from the period 01 January 2006, to 31 January 2019. An infectious event was defined as an outpatient prescription of antimicrobials or a positive diagnostic test for infection. Results: During a period of 5,120 observation-years, we observed 1,394 events in 593 patients. The mean number of infectious events per 100 person-years was 27.2 (standard deviation [SD]: 0.46). There were no differences in mean incidence rates between patients treated with no immunosuppression (23.0 events per 100 person-years, SD: 50.4), patients treated with IM monotherapy (27.6 events per 100 person-years, SD: 49.9), patients treated with anti-TNF monotherapy (34.3 events per 100 person-years, SD: 50.1) and patients on combination therapy (22.5 events per 100-person-years, SD: 44.2). In a multivariate logistic regression, female gender (adjusted odds ratio [AOR]: 2.24; 95% confidence interval [CI]: 1.49–3.37) and combination therapy (AOR: 3.46; 95% CI: 1.52–7.85) were associated with higher risks of infection (>32 events per 100 person years). Also, patients treated with any immunosuppression treatment for 25–75% (AOR: 2.29; 95% CI: 1.21–4.34) and for >75% (AOR: 1.93; 95% CI: 1.19–3.12) of the observation period were at higher risks compared to patients treated with immunosuppression <25% of the observation period. Conclusion: We observed no significant difference in risk for infections between patients on monotherapy with IM or anti-TNF and patients with low use of immunosuppression, but there was a significant risk for combination therapy.

Central Nervous System Demyelination Related to Tumour Necrosis Factor Alpha Inhibitor

Background An association between tumour necrosis factor alpha (TNF-α) inhibitors exposure and central nervous system (CNS) demyelinating disorders has been postulated but is poorly understood. Objectives Describe the clinical spectrum and progress of a cohort of patients who developed demyelinating disorder following exposure to TNF-α inhibitor. Methods Retrospective chart review of patients who presented to a single neurologist in Western Australia between May 2003 and July 2020. Results 7 patients (6 females and 1 male) were identified. Mean age was 49.1 years. Mean follow-up time was 2.9 years. Mean interval between commencement of TNF-α inhibitor and onset of demyelinating event was 3 years. The spectrum of demyelinating events included transverse myelitis ( N = 3), acute brainstem syndrome ( N = 1) and optic neuritis ( N = 1). 2 patients had an atypical presentation but had MRI findings which unequivocally showed demyelinating changes. 2 patients had a monophasic event while the other 5 patients were diagnosed to have multiple sclerosis. All symptomatic patients with multiple sclerosis were started on disease modifying therapy and remained relapse free during follow-up. Conclusion Exposure to TNF-α inhibitor appears to increase the risk of demyelinating event. Whether TNFα inhibition directly results in CNS demyelination or trigger demyelination in susceptible individuals requires further research.

Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 Gene

This study aims at evaluating the ameliorative role of Terminalia catappa aqueous leaf extract (TCA) on hyperglycaemia-induced oxidative stress and inflammation in a high-fat, low dose streptozotocin-induced type 2 diabetic rat model. Experimental rats were treated orally with 400 and 800 mg/kg bw TCA daily for four weeks. Antioxidant enzyme activities, plasma glucose concentration, protein concentration, oxidative stress, and inflammation biomarkers were assayed using standard methods. Hepatic relative expressions of tumour necrosis factor-alpha (TNF-α), interleukin-six (IL-6), and nuclear factor-erythroid 2 related factor 2 (Nrf-2) were also assessed. Molecular docking and prediction of major TCA phytoconstituents’ biological activity related to T2DM-induced oxidative stress were evaluated in silico. Induction of diabetes significantly ( p < 0.05 ) reduced superoxide dismutase, glutathione-S-transferase, and peroxidase activities. Glutathione and protein stores were significantly ( p < 0.05 ) depleted, while glucose, MDA, interleukin-six (IL-6), and tumour necrosis factor-α (TNF-α) concentrations were significantly ( p < 0.05 ) increased. A significant ( p < 0.05 ) upregulation of hepatic TNF-α and IL-6 expression and downregulation ( p < 0.05 ) of Nrf-2 expression were observed during diabetes onset. TCA treatment significantly ( p < 0.05 ) modulated systemic diabetic-induced oxidative stress and inflammation, mRNA expression dysregulation, and dysregulated macromolecule metabolism. However, only 800 mg/kg TCA treatment significantly ( p < 0.05 ) downregulated hepatic TNF-α expression. 9-Oxabicyclo[3.3.1]nonane-2,6-diol and 1,2,3-Benzenetriol bound comparably to glibenclamide in Nrf-2, IL-6, and TNF-α binding pockets. They were predicted to be GST A and M substrate, JAK2 expression, ribulose-phosphate 3-epimerase, NADPH peroxidase, and glucose oxidase inhibitors. These results suggest that TCA ameliorates hyperglycaemia-induced oxidative stress and inflammation by activating Nrf-2 gene.

Incidence of COVID-19 in patients treated with infliximab compared with patients treated with rituximab

ObjectiveTo determine whether patients with inflammatory autoimmune diseases treated with rituximab (RTX) have more severe forms of COVID-19 compared with patients treated with anticytokine therapies, such as Tumour Necrosis Factor (TNF) inhibitors.MethodsWe included all patients who were on either RTX or infliximab (IFX) in two Swiss cantons during the first wave of the COVID-19 pandemic. We collected self-reported symptoms compatible with COVID-19, PCR-confirmed diagnoses of COVID-19 and the evolution of COVID-19 infections. We computed the raw and propensity score-adjusted incidence of COVID-19 by treatment group.Results190 patients were enrolled, of whom 121 (64%) were in the RTX group and 69 (36%) were in the IFX group. Twenty-one patients (11%) reported symptoms compatible with COVID-19 (RTX: 10, IFX: 11, p=0.14). Among patients with COVID-19 symptoms, four developed severe forms of the disease, with life-threatening pulmonary manifestations requiring intensive mechanical ventilation (RTX: 4 of 10, IFX: 0 of 11, Fisher’s exact test p=0.04). The incidence rate of COVID-19 symptoms was 0.73 (95% CI 0.39 to 1.37) cases per 1000 patient-days on RTX vs 1.52 (95% CI 0.82 to 2.85) cases per 1000 patient-days on IFX (crude p=0.10, adjusted p=0.07). The incidence rate of severe COVID-19 was 0.28 (95% CI 0.08 to 0.7.2) cases per 1000 patient-days on RTX compared with null on IFX (95% CI 0.0 to 0.44) (p=0.13). A replication in an independent validation cohort confirmed these findings, with consistent results in the Swiss Clinical Quality Management registry.ConclusionWhile the incidence of symptoms compatible with COVID-19 was overall similar in patients receiving RTX or IFX, the incidence of severe COVID-19 tended to be higher in the RTX group.

Roles of Tumor Necrosis Factor-α and Tumor Necrosis Factor-α Receptor 2 in Inflammation-Related Diseases

The aim of the present review is to provide basic knowledge about the role of tumour necrosis factor-α 1 and tumor necrosis factor-α receptor 2 in neuro-inflammation diseases. We performed an open-ended, English restricted search of PubMed, Embase, PsychINFO, Web of Science, Scopus, and the Cochrane Library for available literature from 24Feb. 2018–12 May 2021, using terms related to neuroinflammation, tumour necrosis factor-α, tumour necrosis factor II (TNFR-II), TNF-α and related diseases, TNFR-II and inflammation-related diseases, their relationships, and polymorphism. The main outcomes assessed were the presence of plaques and tangles, behaviour and cognition, reduction in brain tissue mass, and synaptic function the majority of studies were documented a beneficial effect in other areas, including the presence of plaques and tangles and synaptic function. The human studies were showed that TNF-αI was beneficial to Alzheimer's disease patients, with one being a small pilot study and the latter being an observational study, with a high risk of bias. It is concluded that the functions and mechanisms of TNF-α and TNFR-II in inflammation-related diseases will provide new viewpoints and theories in the development and treatment of these diseases. They play important roles in the pathogenesis of diseases induced by or related to inflammatory cytokines and signaling pathways.