Platelet transfusion in patients with liver cirrhosis crosstalk with neutrophil: Prospective study

ABSTRACT Introduction: Immune dysfunction and thrombocytopenia are common features in liver cirrhosis. Platelet transfusion is the most widely used therapeutic approach for thrombocytopenia when indicated. The transfused platelets are prone to lesions during their storage that empower their interaction with the recipient leucocyte. These interactions modulate the host immune response. The impact of platelet transfusion on the immune system in cirrhotic patients is little understood. Therefore, this study aims to investigate the impact of platelet transfusion on neutrophil function in cirrhotic patients. Methods: This prospective cohort study was implemented on 30 cirrhotic patients receiving platelet transfusion and 30 healthy individuals as a control group. EDTA blood samples were collected from cirrhotic patients before and after an elective platelet transfusion. Flowcytometric analysis of neutrophil functions (CD11b expression and PCN formation) was performed. Results: There was a significant increase in expression of CD11b on neutrophils and Frequency of platelet-complexed neutrophils (PCN) in patients with cirrhosis compared with controls. Platelet transfusion increased level of CD11b and the frequency of PCN even more. There was a significant positive correlation between change in PCN Frequency pefore and after transfusion and the change in expression of CDllb among cirrhotic patients. Conclusions: Elective platelet transfusion appears to increase level of PCN in cirrhotic patients, moreover, exacerbate the expression of activation marker CDllb on both neutrophils and PCN. More research and studies are needed to corroborate our preliminary findings.

Platelet transfusion in patients with liver cirrhosis cross-talk with neutrophil: Prospective study.

INTRODUCTION: Immune dysfunction and thrombocytopenia are common features in liver cirrhosis. Platelet transfusion is the most widely used therapeutic approach for thrombocytopenia when indicated. The transfused platelets are prone to lesions during their storage that empower their interaction with the recipient leucocyte. These interactions modulate the host immune response. The impact of platelet transfusion on the immune system in cirrhotic patients is little understood. Therefore, this study aims to investigate the impact of platelet transfusion on neutrophil function in cirrhotic patients. METHODS: This prospective cohort study was implemented on 30 cirrhotic patients receiving platelet transfusion and 30 healthy individuals as a control group. EDTA blood samples were collected from cirrhotic patients before and after an elective platelet transfusion. Flowcytometric analysis of neutrophil functions (CD11b expression and PCN formation) was performed. RESULTS: There was a significant increase in expression of CD11b on neutrophils and Frequency of platelet-complexed neutrophils (PCN) in patients with cirrhosis compared with controls. Platelet transfusion increased level of CD11b and the frequency of PCN even more. There was a significant positive correlation between change in PCN Frequency pefore and after transfusion and the change in expression of CD11b among cirrhotic patients. CONCLUSIONS: Elective platelet transfusion appears to increase level of PCN in cirrhotic patients, moreover, exacerbate the expression of activation marker CD11b on both neutrophils and PCN. More research and studies are needed to corroborate our preliminary findings.

Theophylline: Old Drug in a New Light, Application in COVID-19 through Computational Studies.

Theophylline (3-methyxanthine) is a historically prominent drug used to treat respiratory diseases, alone or in combination with other drugs. The rapid onset of the COVID-19 pandemic urged the development of effective pharmacological treatments to directly attack the development of new variants of the SARS-CoV-2 virus and possess a therapeutical battery of compounds that could improve the current management of the disease worldwide. In this context, theophylline, through bronchodilatory, immunomodulatory, and potentially antiviral mechanisms, is an interesting proposal as an adjuvant in the treatment of COVID-19 patients. Nevertheless, it is essential to understand how this compound could behave against such a disease, not only at a pharmacodynamic but also at a pharmacokinetic level. In this sense, the quickest approach in drug discovery is through different computational methods, either from network pharmacology or from quantitative systems pharmacology approaches. In the present review, we explore the possibility of using theophylline in the treatment of COVID-19 patients since it seems to be a relevant candidate by aiming at several immunological targets involved in the pathophysiology of the disease. Theophylline down-regulates the inflammatory processes activated by SARS-CoV-2 through various mechanisms, and herein, they are discussed by reviewing computational simulation studies and their different applications and effects.

Possible Beneficial Actions of Caffeine in SARS-CoV-2.

The COVID-19 pandemic has established an unparalleled necessity to rapidly find effective treatments for the illness; unfortunately, no specific treatment has been found yet. As this is a new emerging chaotic situation, already existing drugs have been suggested to ameliorate the infection of SARS-CoV-2. The consumption of caffeine has been suggested primarily because it improves exercise performance, reduces fatigue, and increases wakefulness and awareness. Caffeine has been proven to be an effective anti-inflammatory and immunomodulator. In airway smooth muscle, it has bronchodilator effects mainly due to its activity as a phosphodiesterase inhibitor and adenosine receptor antagonist. In addition, a recent published document has suggested the potential antiviral activity of this drug using in silico molecular dynamics and molecular docking; in this regard, caffeine might block the viral entrance into host cells by inhibiting the formation of a receptor-binding domain and the angiotensin-converting enzyme complex and, additionally, might reduce viral replication by the inhibition of the activity of 3-chymotrypsin-like proteases. Here, we discuss how caffeine through certain mechanisms of action could be beneficial in SARS-CoV-2. Nevertheless, further studies are required for validation through in vitro and in vivo models.

Pectin from Brassica oleracea var. italica triggers immunomodulating effects in vivo.

The immunomodulatory ability of pectins is related with structural features such as the degree of methyl-esterification and branching, as well as the molecular mass. The pectin FB, extracted from broccoli stalks (Brassica oleracea var. italica) had low molecular mass, 56% methyl-esterification and galactose as the main neutral sugar, sharing some characteristics with the modified citrus pectin (MCP), which has been extensively studied in vivo and in vitro due its immunomodulator potential. Considering that broccoli has an important role in the diet, the main objective of this study was to investigate the ability of FB in modulating the immune system in vivo. At concentrations 100-500 µg/mL, FB did not affect the viability of macrophages. Evaluations on morphology and phagocytic activity showed that FB (500 µg/mL) increased the number of activated macrophages by 39% and phagocytic activity by 30% within 48 h. FB (200 mg/kg) administered intraperitoneally increased the number of peritoneal macrophages in mice by 490% after 24 h and modulated these cells for an activated phenotype. In mice, oral administration of FB (200 mg/kg) stimulated lymphocytes from spleen and bone marrow proliferation. FB did not induce nitric oxide (NO) production by macrophages and also did not affect the levels of pro-inflammatory interleukins IL-1ß and IL-12 by peritoneal macrophages, but induced the production of the anti-inflammatory interleukin IL-10. The results could suggest that the anti-inflammatory effects triggered by FB could be related to its degree of esterification and pointed this polysaccharide as a target for the development of new immunomodulatory drugs.

Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-γ, IL-6, IL-17F and IL-22 in PBMCs from Rheumatoid Arthritis Patients.

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic and inflammatory disease that affects about 1% of the world's population. Almost 70% of RA patients have a cardiovascular disease such as Systemic Arterial Hypertension (SAH). Inflammatory cytokines are clearly involved in the pathogenesis of RA and correlated with SAH. OBJECTIVE: It is necessary to understand whether the antihypertensive drugs have a dual effect as immunomodulators and which one is the best choice for RA SAH patients. METHODS: Peripheral Blood Mononuclear Cells (PBMCs) from 16 RA patients were purified and stimulated or not stimulated with anti-CD3 and anti-CD28 mAB and were treated with Enalapril, Losartan and Valsartan at 100µM. Patients were evaluated for clinical and laboratory variables including measures of disease activity by Clinical Disease Activity Index (CDAI) and Disease Activity Score (DAS28). Cytokines were quantified by ELISA sandwich. RESULTS: Losartan was able to reduce levels of IFN-γ (p = 0.0181), IL-6 (p = 0.0056), IL-17F (0.0046) and IL-22 (p = 0.0234) in RA patients. In addition, patients in remission and mild score (DAS28<3.2 and CDAI<10) had a better response to treatment. On the other hand, patients in moderate and severe activity had poor response to Losartan in cytokine inhibition. CONCLUSION: PBMCs from RA patients are responsive in inhibiting proinflammatory cytokines using Losartan better than Enalapril and Valsartan and it could be a better antihypertensive choice for patients with RA and systemic arterial hypertension treatment.

An Immunomodulatory Peptide Confers Protection in an Experimental Candidemia Murine Model.

Fungal Candida species are commensals present in the mammalian skin and mucous membranes. Candida spp. are capable of breaching the epithelial barrier of immunocompromised patients with neutrophil and cell-mediated immune dysfunctions and can also disseminate to multiple organs through the bloodstream. Here we examined the action of innate defense regulator 1018 (IDR-1018), a 12-amino-acid-residue peptide derived from bovine bactenecin (Bac2A): IDR-1018 showed weak antifungal and antibiofilm activity against a Candida albicans laboratory strain (ATCC 10231) and a clinical isolate (CI) (MICs of 32 and 64 µg · ml-1, respectively), while 8-fold lower concentrations led to dissolution of the fungal cells from preformed biofilms. IDR-1018 at 128 µg · ml-1 was not hemolytic when tested against murine red blood cells and also has not shown a cytotoxic effect on murine monocyte RAW 264.7 and primary murine macrophage cells at the tested concentrations. IDR-1018 modulated the cytokine profile during challenge of murine bone marrow-derived macrophages with heat-killed C. albicans (HKCA) antigens by increasing monocyte chemoattractant protein 1 (MCP-1) and interleukin-10 (IL-10) levels, while suppressing tumor necrosis factor alpha (TNF-α), IL-1ß, IL-6, and IL-12 levels. Mice treated with IDR-1018 at 10 mg · kg-1 of body weight had an increased survival rate in the candidemia model compared with phosphate-buffered saline (PBS)-treated mice, together with a diminished kidney fungal burden. Thus, IDR-1018 was able to protect against murine experimental candidemia and has the potential as an adjunctive therapy.