Evaluation of Microparticulate Ovarian Cancer Vaccine via Transdermal Route of Delivery

Ovarian cancer is the fifth most commonly occurring malignancy in women, with the highest mortality rate among all the gynecological tumors. Microparticulate vaccine can serve as an immunotherapeutic approach with a promising antigenic delivery system without a need for conventional adjuvants. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared by spray drying. Further, the effect of interleukins (ILs) such as IL-2 and IL-12 was evaluated in a separate study group by administering them with vaccine particles to enhance the immune response. The vaccine microparticles were administered to C57BL/6 female mice via transdermal alone and in combination with the oral route. The transdermal vaccine was delivered using a metallic microneedle device, AdminPen™. Orally administered microparticles also included an M-cell targeting ligand, Aleuria aurantia lectin, to enhance the targeted uptake from microfold cells (M-cells) in Peyer\u27s patches of small intestine. In case of combination of routes, mice were given 5 transdermal doses and 5 oral doses administered alternatively, beginning with transdermal dose. At the end of vaccination, mice were challenged with live tumor cells. Vaccine alone resulted in around 1.5 times tumor suppression in case of transdermal and combination of routes at the end of 15th week when compared to controls. Inclusion of interleukins resulted in 3 times tumor suppression when administered with transdermal vaccine and around 9 times tumor suppression for the combination route of delivery in comparison to controls. These results were further potentiated by serum IgG, IgG1 and IgG2a titers. Moreover, CD8+ T-cell, CD4+ T-cell and NK (natural killer) cell populations in splenocytes were elevated in case of vaccinated mice. Thus, vaccine microparticles could trigger humoral as well as cellular immune response when administered transdermally and via combination of route of delivery. However overall, vaccine administered with interleukins, via combination of route, was found to be the most efficacious to suppress the tumor growth and lead to a protective immune response

Changes of Interleukins in Patients with Nosocomial Pneumonia Against a Background of Traumatic Brain Injury: Role in the Diagnosis and Monitoring of Disease

Introduction. Nosocomial pneumonia (NP) is the second leading frequency and mortality among nosocomial infections. NP is a frequent complication of severe traumatic brain injury (TBI). The difficulty in diagnosis and monitoring of disease NP on the background of TBI is that the usual signs NP "masked" manifestations of the underlying disease.The aim of our study was to improve the diagnosis and assess the effectiveness of the treatment of nosocomial pneumonia with clarithromycin by studying of serum interleukins in patients with nosocomial pneumonia on the background of traumatic brain injury.Materials and methods. We determined levels of TNFα, IL-4, IL-6, IL-8, IL-10. We examined 45 patients with isolated TBI, 44 patients with NP (standard treatment scheme), 49 patients with NP, each therapy with clarithromycin. The control group was 33 relatively healthy people.Conclusions. The study revealed a significant increase in the concentration of interleukin TNFα, IL-6, IL-8, IL-10 in the serum of patients with NP on the background of TBI compared with patients with isolated TBI and healthy individuals. Our study found significantly lower concentrations of interleukin TNFα, IL-6, IL-8, IL-10 in the serum of patients after treatment with the addition of clarithromycin compared with patients with standard therapy

Role of genetic aspect in pathogenesis of atopic dermatitis

The pathogenesis of atopic dermatitis (AD) is a very complicated process that involves an intricate array of molecules. Nowadays it is generally accepted that cytokines play an important role in the progression of the clinical presentation of atopic dermatitis. However, emerging data point to the possible involvement of cornified envelope proteins in the development of skin barrier dysfunction and illness. Unfortunately, our knowledge on relation of particular genotype to progression of AD is very limited. Therefore, intensive studies are needed to increase our understanding of genetic background of atopic dermatitis. Hopefully the future research will identify new factors that help us to determine the additional risk for certain patients with atopic dermatitis

Mechanisms altering airway smooth muscle cell Ca(2+) homeostasis in two asthma models

Background: Asthma is characterized by airway remodeling, altered mucus production and airway smooth muscle cell (ASMC) contraction causing extensive airway narrowing. In particular, alterations of ASMC contractility seem to be of crucial importance. The elevation of the cytoplasmic Ca(2+) concentration is a key event leading to ASMC contraction and changes in the agonist- induced Ca(2+) increase in ASMC have been reported in asthma. Objective: The aim of this study was to investigate mechanisms underlying these changes. Methods: Murine tracheal smooth muscle cells (MTSMC) from T- bet KO mice and human bronchial smooth muscle cells (HBSMC) incubated with IL-13 and IL-4 served as asthma models. Acetylcholine- induced changes in the cytoplasmic Ca(2+) concentration were recorded using fluorescence microscopy and the expression of Ca(2+) homeostasis regulating proteins was investigated with Western blot analysis. Results: Acetylcholine- induced Ca(2+) transients were elevated in both asthma models. This correlated with an increased Ca(2+) content of the sarcoplasmic reticulum (SR). In MTSMC from T-bet KO mice, the expression of the SR Ca(2+) buffers calreticulin and calsequestrin was higher compared to wild- type mice. In HBSMC incubated with IL-13 or IL-4, the expression of ryanodine receptors, inositol-3-phosphate receptors and sarcoplasmic/ endoplasmic reticulum Ca 2+ ATPases 2 was increased compared to HBSMC without incubation with interleukins. The enlarged acetylcholine- induced Ca(2+) transients could be reversed by blocking inositol-3- phosphate receptors. Conclusions: We conclude that in the murine asthma model the SR Ca(2+) buffer capacity is increased, while in the human asthma model the expression of SR Ca(2+) channels is altered. The investigation of the Ca(2+) homeostasis of ASMC has the potential to provide new therapeutical options in asthma. Copyright (C) 2008 S. Karger AG, Basel

Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection.

Background: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and β-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection

The Relationship Between Serum Levels of Interleukins 6, 8, 10 and Clinical Outcome in Patients With Severe Traumatic Brain Injury

Background: Clinical outcome in patients with severe traumatic brain injury (TBI) depends on both primary and secondary brain injuries. Neuroinflammation is an important secondary mechanism, which occurs by releasing interleukins (ILs). Increased levels of ILs may affect clinical outcome following TBI. Objectives: This study aimed to determine the relationship between the serum levels of interleukins 6, 8 and 10 and clinical outcome in patients with severe TBI 6 months after injury. Patients and Methods: In a descriptive-analytical study, 44 patients with GCS ≤ 8 (Glasgow coma scale) and age ≥ 14 years were included. Their blood samples were collected at first 6 hours after injury. Clinical outcome was determined based on GOS (Glasgow Outcome Scale) at 6 months after head injury. Serum levels of interleukins 6, 8 and 10 were measured using the ELISA method. Spearman's rho, independent T-Test, and Mann-Whitney Test were used for data analysis. Results: Comparing the serum levels of interleukins in two groups with favorable and unfavorable clinical outcomes showed that the mean serum levels of interleukins 6 and 8 in group with favorable outcome was 85.2 ± 51.6 and 52.2 ± 31.9, respectively lower than those of group with unfavorable outcome with 162.3 ± 141.1 and 173.6 ± 257.3 (P < 0.03) and (P < 0.01). Conclusions: Increased serum levels of interleukins 6 and 8 as a predictive marker might be associated with unfavorable clinical outcome in patients with severe TBI

IL-13R alpha 2 reverses the effects of IL-13 and IL-4 on bronchial reactivity and acetylcholine-induced Ca2+ signaling

Background: The interleukins IL-4 and IL-13 play a key role in the pathophysiology of asthma. The interleukin receptor IL-13R alpha 2 is believed to act as a decoy receptor, but until now, the functional significance of IL-13R alpha 2 remains vague. Methods: Bronchial reactivity was quantified in murine lung slices by digital video microscopy and acetylcholine (ACH)-induced Ca2+ signaling was measured in human airway smooth muscle cells (ASMC) using fluorescence microscopy. Results: IL-4 or IL-13 up to 50 ng/ml induced bronchial hyperreactivity. But after incubation with 100 ng/ml this effect was lost and bronchial responsiveness was again comparable to the control level. The effects of IL-4 and IL-13 on bronchial reactivity were paralleled by the effects on ASMC proliferation. Fifty nanograms per milliliter of IL-4 and IL-13 increased the Ca2+ response of human ASMC to ACH. At 100 ng/ml, however, the effects of the cytokines on the Ca2+ response were no longer evident. The expression of IL-13R alpha 2 increased with increasing concentrations of IL-4 or IL-13, reaching its maximum at 100 ng/ml. Blocking IL-13R alpha 2, the loss of the effect of IL-4 and IL-13 at 100 ng/ml on human ASMC proliferation and the ACH-induced Ca2+ response were no longer present. Conclusions: IL-4 and IL-13 induce bronchial hyperreactivity by changing the Ca2+ homeostasis of ASMC. These effects are counteracted by IL-13R alpha 2. The biological significance of IL-13R alpha 2 might be a protective function by regulating IL-13- and IL-4-mediated signal transduction and thereby limiting pathological alterations in Th2-mediated inflammatory diseases. Copyright (c) 2007 S. Karger AG, Basel

Expression of Interleukin-1 and Temporomandibular Disorder: Contemporary Review of the Literature

Objective: Temporomandibular disorders (TMD) are a group of conditions affecting the temporomandibular joint (TMJ), leading to jaw dysfunction, joint and muscle pain, and a decrease in quality of life. A communication network of pro- and anti-inflammatory mediators called cytokines maintains the homeostasis of the TMJ. This review will focus on the Interleukin (IL) family of cytokines, which have been quantified in TMJ synovial fluids in a variety of studies. IL-1α and IL-1β have pro-inflammatory effects, while the endogenous receptor antagonist (IL-1RA) inhibits the pro-inflammatory effects of IL-1. Methods: A literature search (2006–2016) to identify eligible studies was completed using the PubMed database. Studies identified used saline irrigation to quantify cytokine profiles in synovial fluid of healthy and/or dysfunctional joints. Results: The initial search yielded 111 articles, 5 of which met the inclusion criteria after inter-reviewer discussion. Conclusions: Articles that compared IL-1 concentrations in TMD vs. control groups found significant differences