cytokine therapy
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2021 ◽  
Vol 21 (1) ◽  
Author(s):  
O. V. Stanevich ◽  
D. S. Fomina ◽  
I. G. Bakulin ◽  
S. I. Galeev ◽  
E. A. Bakin ◽  
...  

Abstract Background Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib. Methods The matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020. Results Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6–14.6%]) vs 13.0% (95% CI [7.5–18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31–1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11–1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8–16 mg dexamethasone). Conclusions Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration. Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date


Cell Reports ◽  
2021 ◽  
Vol 37 (8) ◽  
pp. 110021
Author(s):  
Chensu Wang ◽  
Ang Cui ◽  
Maurice Bukenya ◽  
Aereas Aung ◽  
Dikshant Pradhan ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1566
Author(s):  
Christian R. Pangilinan ◽  
Che-Hsin Lee

Bacteria-mediated cancer therapy (BMCT) is an emerging tool that may advance potential approaches in cancer immunotherapy, whereby tumors are eradicated by the hosts’ immune system upon recruitment and activation by bacteria such as Salmonella. This paper provides an emphasis on the immunomodulatory effects that encompasses both the innate and adaptive immune responses inherently triggered by Salmonella. Furthermore, modifications of Salmonella-based treatment in the attempt to improve tumor-specific immune responses including cytokine therapy, gene therapy, and DNA vaccine delivery are likewise discussed. The majority of the findings described herein incorporate cell-based experiments and murine model studies, and only a few accounts describe clinical trials. Salmonella-based cancer therapy is still under development; nonetheless, the pre-clinical research and early-phase clinical trials that have been completed so far have shown promising and convincing results. Certainly, the continuous development of, and innovation on, Salmonella-based therapy could pave the way for its eventual emergence as one of the mainstream therapeutic interventions addressing various types of cancer.


2021 ◽  
Vol 25 (1) ◽  
pp. 27-35
Author(s):  
J. V. Kosayev ◽  
I. A. Khasanov ◽  
N. S. Abushov ◽  
G. T. Taghi-zade

Aim: to study the state of lipid metabolism, hemostasis, inflammatory reaction and the potential for their correction after indirect revascularization in patients with distal steno-occlusion of arteries and critical ischemia of lower extremities (critical ILE).Material and methods. Changes in hemostasis and dynamics of its parameters during the complex surgical treatment in 131 patients with critical ILE and distal arterial stenoocclusion were analyzed. To achieve the targeted goals, patients were divided into the following groups: 34 patients had traditional care (control group); 32 patients had intravenous laser blood irradiation in combination with standard therapy (Group I); 32 patients had cytokine therapy with roncoleukin in combination with standard therapy (Group II); 33 patients had intravenous laser blood irradiation combined with cytokine therapy and standard therapy (Group III). Parameters of lipid metabolism were studied in dynamics (total cholesterol, very low density lipoproteins, high density lipoproteins, triglycerides); products of lipid peroxidation (malondialdehydes, conjugates, superoxide dismutase); inflammatory mediators (C-reactive protein, sialic acids, seromucoids, fibrinogen A, circulating immune complexes); hemostatic parameters (fibrinogen, fibrinolytic activity, fibrin degradation products, antithrombin III activity). Hemostatic indices were compared with identical parameters of 48 apparently healthy individuals (reference group).Results. On admission, patients with critical ILE and distal wall occlusion had sharp changes in their lipid metabolism, inflammatory reaction, and hemostasis. Conclusion. The inclusion of intravenous laser blood irradiation and cytokine therapy separately and in combination in a set of therapeutic measures led to the leveling of the studied homeostasis indicators. The best results were obtained in the group where patients had combined perioperative intravenous laser blood irradiation with cytokine therapy in indirect revascularization.


Author(s):  
Aslan Mansurov ◽  
Abigail Lauterbach ◽  
Erica Budina ◽  
Aaron T. Alpar ◽  
Jeffrey A. Hubbell ◽  
...  

Since the discovery of cytokines, much effort has been put forth to achieve therapeutic translation for treatment of various diseases, including cancer and autoimmune diseases. Despite these efforts, very few cytokines have cleared regulatory approval, and those that were approved are not commonly used due to their challenging toxicity profile and/or limited therapeutic efficacy. The main limitation in translation has been that wild-type cytokines have unfavorable pharmacokinetic and pharmacodynamic profiles, either eliciting unwanted systemic side effects or insufficient residence in secondary lymphoid organs. In this review, we address protein engineering approaches that have been applied to both pro- and anti-inflammatory cytokines to enhance their therapeutic indices, and we highlight diseases in which administration of engineered cytokines is especially relevant.


2021 ◽  
pp. 31-40
Author(s):  
M.R. Orazov ◽  
L.M. Mikhaleva ◽  
E.S. Silantieva ◽  
R.E. Orekhov

Recent evidence indicates that the endometrium plays a much more important role in successful implantation and clinical pregnancy than many other recognized factors. Chronic endometritis (CE) is associated with negative reproductive outcomes, including repeated implantation failures. Streptococcus spp., Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus spp., Corynebacterium and Mycoplasma / Ureaplasmaspp are currently considered the main pathogens of CE. This disease disrupts the architectonics of the endometrium at different levels: first of all, CE promotes changes in the population of immunocompetent cells and, therefore, contributes to the disruption of the local immune response in the endometrium at the time of implantation. Antibiotic treatment for CE improves implantation rates and decreases abortion rates, although there are no well-designed prospective studies to support this conclusion. Considering the insufficient effectiveness of antibiotic therapy for CE, especially in cases of resistance of pathogens, or in the case of viral chronic endometritis, it is necessary to develop schemes with additional use of drugs that affect other etiopathogenetic pathways of development and maintenance of CE. An example of such a treatment can be cytokine therapy, which requires further study regarding the efficacy and safety in CE therapy.


Author(s):  
M.S. Denisko ◽  
◽  
O.I. Krivosheina ◽  

Goal. To study the features of the local cytokine profile of patients with secondary corneal dystrophy of various etiologies. Material and methods. The study was conducted among 4 patients: 1 – with bullous kerathopathy, 1 – with secondary postherpetic corneal dystrophy, 1 – with secondary keratectasia and 1 – with secondary corneal dystrophy of neurogenic origin. The quantitative content of cytokines in the lacrimal fluid was studied: interleukin (IL) 1β, 6, 4, 10, transforming growth factor β2 (TGF-β2). Results. All patients had in 3.0-4.3-fold increase in IL-1β and a 2.0-4.1-fold increase in IL-6. In bullous kerathopathy and secondary corneal dystrophy of neurogenic origin, there was in 1.1-and 1.2-fold increase in IL-4 in both cases, and a slight increase in IL-10 and TGF-β2. At the same time, in secondary keratectasia and secondary postherpetic corneal dystrophy, there was a decrease in the level of these cytokines: IL-4 by 1.7 and 1.3 times, respectively, IL-10 by 1.2 times in both cases, and TGF-β2 by 1.5 and 1.3 times, respectively. Conclusion. The study of the local cytokine profile in patients with secondary corneal dystrophy of different etiologies indicates the presence of similar aspects of pathogenesis, which is of some interest and deserves further study. The obtained results open up prospects for the development of personalized cytokine therapy for secondary corneal dystrophy of various etiologies. Key words: secondary corneal dystrophy, immunology, cytokines.


2021 ◽  
Vol 8 ◽  
Author(s):  
Thomas Tao-Min Huang ◽  
Ying-Chun Chien ◽  
Chih-Hsien Wang ◽  
Sui-Yuan Chang ◽  
Jann-Tay Wang ◽  
...  

The COVID-19 pandemic has caused multiple deaths worldwide. Since no specific therapies are currently available, treatment for critically ill patients with COVID-19 is supportive. The most severe patients need sustained life support for recovery. We herein describe the course of a critically ill COVID-19 patient with multi-organ failure, including acute respiratory failure, acute kidney injury, and fulminant cytokine release syndrome (CRS), who required mechanical ventilation and extracorporeal membrane oxygenation support. This patient with a predicted high mortality risk was successfully managed with a careful strategy of oxygenation, uremic toxin removal, hemodynamic support, and most importantly, cytokine-targeted intervention for CRS, including cytokine/endotoxin removal, anti-cytokine therapy, and immune modulation. Comprehensive cytokine data, CRS parameters, and biochemical data of extracorporeal removal were provided to strengthen the rationale of this strategy. In this report, we demonstrate that timely combined hemoperfusion with cytokine adsorptive capacity and anti-cytokine therapy can successfully treat COVID-19 patients with fulminant CRS. It also highlights the importance of implementing cytokine-targeted therapy for severe COVID-19 guided by the precise measurement of disease activity.


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