Inflammation persists in patients infected with HIV. Reduction of inflammatory cytokines and microbial translocation might be one way that this could be managed. Purpose: The anti-inflammatory properties of certain probiotic strains prompted us to investigate whether a probiotic could reduce the inflammatory index of HIV-infected patients. Methods: The study involved 30 HIV+ males on antiretroviral therapy, who were given one bottle of fermented milk Yakult Light^® containing Lactobacillus casei Shirota (LcS) twice a day for four weeks. Results: The probiotic LcS was associated with an increase of T lymphocytes and a significant increase of CD56+ cells (p = 0.04). There was also a significant decrease of mRNA levels of TGFβ, IL-10 and IL-12 (p < 0.001) and IL-1β expression (p < 0.001) and an increase of serum IL-23 (p = 0.03). In addition, decreased inflammation and cardiovascular risk were observed, as shown by a reduction of cystatin C (p < 0.001). Conclusions: These data provide preliminary evidence that probiotic supplementation may modulate certain immunological parameters and some of the cytokines that were analyzed. Thus, we propose that LcS may be an inexpensive and practical strategy to support the immune function of HIV+ patients.

Background: Clinicians all around the world are currently experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Several therapeutic strategies have been used until now but, to date, there is no specific therapy to treat SARS‐CoV‐2 infection. In this study, we used canakinumab, a human monoclonal antibody targeting interleukin‐1 beta to improve respiratory function and laboratory parameters compared with standard therapy (hydroxycloroquine plus lopinavir/ritonavir).Methods: We enrolled 34 patients with mild or severe non intensive care unit (ICU) coronavirus disease 2019 (COVID‐19): 17 patients treated with standard therapy and 17 patients treated with a subcutaneous single dose of canakinumab 300 mg. We collected data about oxygen supports and laboratory parameters such as inflammation indices and hemogasanalysis. We compared the data collected before the administration of canakinumab (T0), 3 days after T0 (T1) and 7 days after T0 (T2) with the same data from patients taking the standard therapy.Results: We observed a reduction in inflammation indices and a significant and rapid increase in P/F ratio in canakinumab group, with improvement of 60.3% after the administration. We reported a significant reduction in oxygen flow in patients treated with canakinumab (−28.6% at T1 vs. T0 and −40.0% at T2 vs. T1). Conversely, the standard group increased the supply of high oxygen at T1 versus T0 (+66.7%), but reduced oxygen flows at T2 versus T1 (−40.0%).Conclusion: In hospitalized adult patients with mild or severe non ICU COVID‐19, canakinumab could be a valid therapeutic option. Canakinumab therapy causes rapid and long‐lasting improvement in oxygenation levels in the absence of any severe adverse events.

Currently clinicians all around the world are experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical presentation of this pathology includes fever, dry cough, fatigue and acute respiratory distress syndrome that can lead to death infected patients. Current studies on coronavirus disease 2019 (COVID-19) continue to highlight the urgent need for an effective therapy. Numerous therapeutic strategies have been used until now but, to date, there is no specific effective treatment for SARS-CoV-2 infection. Elevated inflammatory cytokines have been reported in patients with COVID-19. Evidence suggests that elevated cytokine levels, reflecting a hyperinflammatory response secondary to SARS-CoV-2 infection, are responsible for multi-organ damage in patients with COVID-19. For these reason, numerous randomized clinical trials are currently underway to explore the effectiveness of biopharmaceutical drugs, such as, interleukin-1 blockers, interleukin-6 inhibitors, Janus kinase inhibitors, in COVID-19. The aim of the present paper is to briefly summarize the pathogenetic rationale and the state of the art of therapeutic strategy blocking hyperinflammation.

Objective: We aimed to investigate the effect of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on the hepatic safety and metabolic profile. Methods: Consecutive HIV patients, enrolled in the Surveillance Cohort Long-term Toxicity Antiretrovirals/Antivirals (SCOLTA) project, switching from TDF to TAF were included. Changes from baseline (T0) to 6-month follow-up (T1) were evaluated using paired t-test and signed rank test. Results: A total of 190 patients switched from TDF to TAF and had one 6-month follow-up visit. They were 80% male, 74.2% at CDC stage A–B, 93.7% with undetectable HIV-viral load. Mean age was 46.7± 10.7 years, body mass index was 25.0± 3.9 kg/m², median CD4 cell count was 634 cell/μL (interquartile range [IQR]=439– 900), aspartate aminotransferase (AST) was 23 (IQR=19– 30) IU/L, and alanine aminotransferase (ALT) was 24 (IQR=17– 34) IU/L. At T1, both AST (median=− 1, IQR=− 5– 2 IU/L, P=0.004) and ALT (median=− 2, IQR=− 7– 3 IU/L, P=0.0004) showed a significant decrease. Among 28 patients with ALT > 40 at baseline, reduction was significant both clinically (− 17, IQR=− 32–− 1) and statistically (P=0.0003). Total cholesterol levels (TC) increased (+13.4± 3.8 mg/dL, P=0.0006), as well as HDL-cholesterol (HDL-C) (+3.8± 1.2 mg/dL, P=0.02), LDL Cholesterol (LDL-C) (+7.6± 3.4, P=0.03) and glucose (+4.0± 1.8 mg/dL, P=0.02). D:A:D: and Framingham risk score did not change at 6 months after switch. Conclusion: A significant reduction of liver enzymes was observed after switching from TDF to TAF, especially in subjects with initial level of ALT > 40 IU/L. Glucose, TC, HDL-C, and LDL-C increased, with no effect on cardiovascular risk scores.

Background: Extracellular vesicles, released by cell pullulation, are surrounded by a phospholipid bilayer and carry proteins as well and genetic material. It has been shown that extracellular vesicles mediate intercellular communication in several conditions, such as inflammation, immunodeficiency, tumor growth, and viral infections. Here, we analyzed circulating levels of extracellular vesicles in order to clarify their role in chronic inflammation mechanisms characterizing HIV patients. Methods: We analyzed and subtyped circulating levels of extracellular vesicles, through a recently developed flow cytometry method. In detail, endothelial-derived extracellular vesicles (CD31⁺/CD41a−/CD45⁻, EMVs), extracellular vesicles stemming from leukocytes (CD45⁺, LMVs) and platelets (CD41a+/CD31⁺) were identified and enumerated. Moreover, we analyzed the extracellular vesicle protein cargo with proteomic analysis. Results: Circulating levels of total extracellular vesicles, EMVs and LMVs were significantly lower in the HIV+ patients than in healthy subjects, whereas platelet-derived extracellular vesicles resulted higher in patients than in the healthy population. Proteomic analysis showed the upregulation of gammaIFN and IL1α, and down-regulation of OSM, NF-kB, LIF, and RXRA signaling resulted activated in this patients. Conclusion: These data demonstrate, for the first time that HIV infection induces the production of extracellular vesicles containing mediators that possibly feed the chronic inflammation and the viral replication. These two effects are connected as the inflammation itself induces the viral replication. We, therefore, hypothesize that HIV infection inhibits the production of extracellular vesicles that carry anti-inflammatory molecules.

Background. Inflammatory responses have been associated with delayed oral mucosal wound healing and the pathogenesis of the periodontal disease. The invasion of microbes into the tissues and the establishment of a chronic infection may be due to impaired healing. The protracted inflammatory phase may delay wound healing and probably support tissue fibrosis and reduce tissue regeneration. Vanillin is a well‐known natural compound with potential anti‐inflammatory capacity. Hence, we hypothesized that Vanillin could accelerate wound healing reducing inflammation and especially cytokine production making the oral tissue repair process easier. Methods. Our hypothesis was tested using primary human gingival fibroblast (HGF) cell pretreated with Vanillin and primed with IL‐1β, as inductor of proinflammatory environment. After 24 hours of treatments, the gene expression and production of IL‐6, TNF‐α, IL‐8, COX‐2, iNOS, and nitric oxide (NO) generation and the wound healing rate were determined. Results. In IL‐1β‐primed cells, preincubation with Vanillin reduced IL‐6, IL‐8, COX‐2, and iNOS expression and NO release, compared to IL‐1β‐primed cells. Moreover, Vanillin determines the increased gene expression of nAChRα7, leading us to hypothesize a role of Vanillin in the activation of the cholinergic anti‐inflammatory pathway. Furthermore, in presence of mechanical injury, the Vanillin preincubation, wound closure may be reducing the expression and release of IL‐6 and TNF‐α and upregulation of COX‐2 and IL‐8. Conclusion. Together, the results of this study highlight the anti‐inflammatory and tissue repair ability of Vanillin in IL‐1β‐primed HGF. Therefore, Vanillin shows a potential therapeutic interest as an inflammatory modulator molecule with novel application in periodontal regeneration and oral health.