scholarly journals Novel Anti-Cytokine Strategies for Prevention and Treatment of Respiratory Allergic Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Ekaterina O. Gubernatorova ◽  
Olga A. Namakanova ◽  
Ekaterina. A. Gorshkova ◽  
Alexandra D. Medvedovskaya ◽  
Sergei A. Nedospasov ◽  
...  

Asthma is a heterogeneous inflammatory disease characterized by airflow obstruction, wheezing, eosinophilia and neutrophilia of the airways. Identification of distinct inflammatory patterns characterizing asthma endotypes led to the development of novel therapeutic approaches. Cytokine or cytokine receptor targeting by therapeutic antibodies, such as anti-IL-4 and anti-IL-5, is now approved for severe asthma treatment. However, the complexity of cytokine networks in asthma should not be underestimated. Inhibition of one pro-inflammatory cytokine may lead to perturbed expression of another pro-inflammatory cytokine. Without understanding of the underlying mechanisms and defining the molecular predictors it may be difficult to control cytokine release that accompanies certain disease manifestations. Accumulating evidence suggests that in some cases a combined pharmacological inhibition of pathogenic cytokines, such as simultaneous blockade of IL-4 and IL-13 signaling, or blockade of upstream cytokines, such as TSLP, are more effective than single cytokine targeting. IL-6 and TNF are the important inflammatory mediators in the pathogenesis of asthma. Preliminary data suggests that combined pharmacological inhibition of TNF and IL-6 during asthma may be more efficient as compared to individual neutralization of these cytokines. Here we summarize recent findings in the field of anti-cytokine therapy of asthma and discuss immunological mechanisms by which simultaneous targeting of multiple cytokines as opposed to targeting of a single cytokine may improve disease outcomes.

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110147
Author(s):  
Tong Li ◽  
Shu-Wei Jia ◽  
Dan Hou ◽  
Xiaoran Wang ◽  
Dongyang Li ◽  
...  

Oxytocin (OT), a neuropeptide produced in the supraoptic (SON) and paraventricular (PVN) nuclei, is not only essential for lactation and maternal behavior but also for normal immunological activity. However, mechanisms underlying OT regulation of maternal behavior and its association with immunity around parturition, particularly under mental and physical stress, remain unclear. Here, we observed effects of OT on maternal behavior in association with immunological activity in rats after cesarean delivery (CD), a model of reproductive stress. CD significantly reduced maternal interests to the pups throughout postpartum day 1-8. On postpartum day 5, CD decreased plasma OT levels and thymic index but increased vasopressin, interleukin (IL)-1β, IL-6 and IL-10 levels. CD had no significant effect on plasma adrenocorticotropic hormone and corticosterone levels. In the hypothalamus, CD decreased corticotropin-releasing hormone contents in the PVN but increased OT contents in the PVN and SON and OT release from hypothalamic implants. CD also increased c-Fos expression, particularly in the cytoplasm of OT neurons. Lastly, CD depolarized resting membrane potential and increased spike width while increasing the variability of the firing rate of OT neurons in brain slices. Thus, CD can increase hypothalamic OT contents and release but reduce pituitary release of OT into the blood, which is associated with depressive-like maternal behavior, increased inflammatory cytokine release and decreased relative weight of the thymus.


2021 ◽  
Vol 22 (9) ◽  
pp. 4676
Author(s):  
Katja Badanjak ◽  
Sonja Fixemer ◽  
Semra Smajić ◽  
Alexander Skupin ◽  
Anne Grünewald

With the world’s population ageing, the incidence of Parkinson’s disease (PD) is on the rise. In recent years, inflammatory processes have emerged as prominent contributors to the pathology of PD. There is great evidence that microglia have a significant neuroprotective role, and that impaired and over activated microglial phenotypes are present in brains of PD patients. Thereby, PD progression is potentially driven by a vicious cycle between dying neurons and microglia through the instigation of oxidative stress, mitophagy and autophagy dysfunctions, a-synuclein accumulation, and pro-inflammatory cytokine release. Hence, investigating the involvement of microglia is of great importance for future research and treatment of PD. The purpose of this review is to highlight recent findings concerning the microglia-neuronal interplay in PD with a focus on human postmortem immunohistochemistry and single-cell studies, their relation to animal and iPSC-derived models, newly emerging technologies, and the resulting potential of new anti-inflammatory therapies for PD.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 817
Author(s):  
Ruth P. Cusack ◽  
Christiane E. Whetstone ◽  
Yanqing Xie ◽  
Maral Ranjbar ◽  
Gail M. Gauvreau

Asthma is a complex and chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, bronchospasm, and airway eosinophilia. As the pathophysiology of asthma is becoming clearer, the identification of new valuable drug targets is emerging. IL-5 is one of these such targets because it is the major cytokine supporting eosinophilia and is responsible for terminal differentiation of human eosinophils, regulating eosinophil proliferation, differentiation, maturation, migration, and prevention of cellular apoptosis. Blockade of the IL-5 pathway has been shown to be efficacious for the treatment of eosinophilic asthma. However, several other inflammatory pathways have been shown to support eosinophilia, including IL-13, the alarmin cytokines TSLP and IL-33, and the IL-3/5/GM-CSF axis. These and other alternate pathways leading to airway eosinophilia will be described, and the efficacy of therapeutics that have been developed to block these pathways will be evaluated.


Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 701
Author(s):  
Aroa Lopez-Santamarina ◽  
Esther Gonzalez Gonzalez ◽  
Alexandre Lamas ◽  
Alicia del Carmen Mondragon ◽  
Patricia Regal ◽  
...  

Allergies are an increasing global public health concern, especially for children and people living in urban environments. Allergies impair the quality of life of those who suffer from them, and for this reason, alternatives for the treatment of allergic diseases or reduction in their symptoms are being sought. The main objective of this study was to compile the studies carried out on probiotics as a possible therapy for allergies. The most studied allergies on which probiotics have been shown to have a beneficial effect are rhinitis, asthma, and atopic dermatitis. Most studies have studied the administration of Lactobacillus and Bifidobacterium spp. in children and have shown beneficial effects, such as a reduction in hyperreactivity and inflammation caused by allergens and a decrease in cytokine release, among other beneficial effects. In the case of children, no clear beneficial effects were found in several studies, and the potential risk from the use of some opportunistic bacteria, such as probiotics, seems controversial. In the studies that reported beneficial results, these effects were found to make allergy symptoms less aggressive, thus reducing morbidity in allergy sufferers. The different effects of the same probiotic bacteria on different patients seem to reinforce the idea that the efficacy of probiotics is dependent on the microbial species or strain, its derived metabolites and byproducts, and the gut microbiota eubiosis of the patient. This study is relevant in the context of allergic diseases, as it provides a broader understanding of new alternatives for the treatment of allergies, both in children, who are the main sufferers, and adults, showing that probiotics, in some cases, reduce the symptoms and severity of such diseases.


2005 ◽  
Vol 19 (4) ◽  
pp. e60-e61
Author(s):  
Lara A. Regis ◽  
Christopher G. Engeland ◽  
Jos A. Bosch ◽  
John T. Cacioppo ◽  
Phillip T. Marucha

Shock ◽  
2007 ◽  
Vol 27 (4) ◽  
pp. 397-401 ◽  
Author(s):  
Abdulkadir Bedirli ◽  
Mustafa Kerem ◽  
Hatice Pasaoglu ◽  
Nalan Akyurek ◽  
Tugan Tezcaner ◽  
...  

2021 ◽  
Vol 9 (A) ◽  
pp. 114-118
Author(s):  
Didit Pramudhito ◽  
Suwandi Sugandi ◽  
Ida Parwati ◽  
Muchtan Sujatno ◽  
Soetojo Soetojo

BACKGROUND: Immunological mechanisms of infertility are still poorly understood and controversial, both the cause and treatment. Inflammation, immunology, cell proliferation, cell differentiation, and cell survival are influenced by several proteins, including nuclear factor kappa-B (NFĸB), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10). AIM: This study aimed to explore the potential of nano curcumin to prevent anti-sperm antibodies (ASA) formation due to the testes’ inflammatory process in Wistar rats. METHODS: This research is an experimental study with a pre-post-test approach with control group. The research subjects were rats (Rattus norvegicus) of the Wistar strain. The induced animals were grouped into three groups: Group 1 received nano curcumin 1 × 80 mg/kg BW orally, Group 2 received dexamethasone 1 × 0.3 mg/kg BW, and Group 3 received placebo aquadest 1 × 1 mL orally. TNF-α, NF-kB, and IL10 levels in serum were examined with enzyme-linked immunosorbent assay. RESULTS: The nano curcumin treatment showed the ability to reduce the pro-inflammatory cytokine protein TNF-α expression (47.3 ± 2.32) more optimally than dexamethasone treatment (54.4 ± 3.22). Nano curcumin has also shown the ability to reduce the pro-inflammatory cytokine transcription factor, NF-kB (32.5 ± 2.76) more optimally than treatment with dexamethasone (44.6 ± 2.43). CONCLUSION: Nano curcumin can prevent the formation of ASA in testicular trauma through inhibition of the inflammatory response.


2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Christopher Thomas Ford ◽  
Sian Richardson ◽  
Francis McArdle ◽  
Alan Crozier ◽  
Anne McArdle ◽  
...  

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