Animal Models Of Inflammation Research Articles

Prostacyclin Regulation of Allergic Inflammation.

Prostacyclin is a metabolic product of the cyclooxygenase pathway that is constitutively expressed and can be induced during inflammatory conditions. While prostacyclin and its analogs have historically been considered effective vasodilators and used in treating pulmonary hypertension, prostacyclin has demonstrated potent anti-inflammatory effects in animal models of allergic airway inflammation. In vitro studies reveal that prostacyclin directly inhibits type 2 cytokine production from CD4+ Th2 cells and ILC2 and reduces the ability of dendritic cells to generate Th2 cytokine production from CD4+ T cells in an antigen-specific manner. Thus, there is strong evidence that prostacyclin may be an additional therapeutic target for treating allergic inflammation and asthma in human subjects.

TGF-β1 contributes to the hepatic inflammation in animal models with nonalcoholic steatohepatitis by Smad3/TLR2 signaling pathway

Non-alcoholic fatty liver disease (NAFLD) is increasingly affecting human health and the economy worldwide due to various factors. Here, we found that the expression of TGF-β1 and TLR2 was significantly up-regulated in liver samples from both rats and mice nonalcoholic steatohepatitis (NASH) models. By constructing corresponding cell model, we found that TGF-β1 challenge can positively regulate the expression of TLR2 and p-Smad2/3, and the dual luciferase reporter gene system and EMSA assay confirmed the existence of Smad3 binding site (−916 ∼ −906) in the promoter region of TLR2. The overexpression and interference changes of Smad2/3 further verified the above experimental results. Taken together, these findings suggest that TGF-β1 promotes TLR2 transcription and its target gene expression via Smad3, leading to malignant exacerbation of liver inflammation in NASH, which provides new insights into the treatment of NASH.

TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner

Children with chronic inflammation are often treated with glucocorticoids (GCs) and many of them experience growth retardation. It is poorly understood how GCs interact with inflammatory cytokines causing growth failure as earlier experimental studies have been performed in healthy animals. To address this gap of knowledge, we used a transgenic mouse model where human TNF is overexpressed (huTNFTg) leading to chronic polyarthritis starting from the first week of age. Our results showed that femur bone length and growth plate height were significantly decreased in huTNFTg mice compared to wild type animals. In the growth plates of huTNFTg mice, increased apoptosis, suppressed Indian hedgehog, decreased hypertrophy, and disorganized chondrocyte columns were observed. Interestingly, the GC dexamethasone further impaired bone growth, accelerated chondrocyte apoptosis and reduced the number of chondrocyte columns in huTNFTg mice. We conclude that TNF and dexamethasone separately suppress chondrogenesis and bone growth when studied in an animal model of chronic inflammation. Our data give a possible mechanistic explanation to the commonly observed growth retardation in children with chronic inflammatory diseases treated with GCs.

Inflammatory Animal Models of Parkinson's Disease.

Accumulating evidence suggests that microglia and peripheral immune cells may play determinant roles in the pathogenesis of Parkinson’s disease (PD). Consequently, there is a need to take advantage of immune-related models of PD to study the potential contribution of microglia and peripheral immune cells to the degeneration of the nigrostriatal system and help develop potential therapies for PD. In this review, we have summarised the main PD immune models. From a historical perspective, we highlight first the main features of intranigral injections of different pro-inflammogens, including lipopolysaccharide (LPS), thrombin, neuromelanin, etc. The use of adenoviral vectors to promote microglia-specific overexpression of different molecules in the ventral mesencephalon, including α-synuclein, IL-1β, and TNF, are also presented and briefly discussed. Finally, we summarise different models associated with peripheral inflammation whose contribution to the pathogenesis of neurodegenerative diseases is now an outstanding question. Illustrative examples included systemic LPS administration and dextran sulfate sodium-induced colitis in rodents.

Formulation of Topical Flurbiprofen Solid Lipid Nanoparticle Gel Formulation Using Hot Melt Extrusion Technique.

Hot melt extrusion (HME) has been used for the formulation of topical solid lipid nanoparticle (SLN) gel without using any other size reduction technique including high pressure homogenization or sonication. SLN formulation solely using HME has not been applied to other drugs except IBU. Therefore, the purpose of the present study was to formulate FLB SLN solely using HME technique and evaluate the SLN formulation in inflammation animal model. Stable 0.5%w/v FLB SLN gel with particle size < 250nm, PI < 0.3 and EE of > 98% was prepared. Differential scanning calorimetry (DSC) thermogram showed that the drug was converted to amorphous form in the HME process. Additionally, rheological studies demonstrated that FLB SLN gel and marketed FLB gel showed shear thinning property. FLB SLN formulation showed significantly (p < 0.05) higher peak force required to spread the formulation as compared to marketed FLB formulation. Stability studies showed that FLB SLN gel was stable for a month at room temperature and 2-4°C. Moreover, in vitro permeation test (IVPT) and ex vivo skin deposition study results revealed that FLB SLN gel showed significant (p < 0.05) increase in drug deposition in dermal layer and drug permeation as compared to control marketed formulation. Further, in vivo anti-inflammatory study showed equivalent inhibition of rat paw edema using 0.5% w/v FLB SLN gel which has 10 times less strength compared to control formulation. Overall, FLB SLN formulation was successfully manufactured solely using HME technique which resulted in enhanced the skin permeation of FLB and superior anti-inflammatory activity.

Structural and functional properties of rBmTI-A: A Kunitz-BPTI serine protease inhibitor with therapeutical potential

Serine proteases are an important group of enzymes present in several organisms such as viruses, bacteria and eukaryotes involved in several physiological and pathological processes such as cancer, neurodegeneration, tissue inflammation and infections. Kunitz-type serine protease inhibitors have been studied as therapeutical targets with positive results in many of these diseases. rBmTI-A (recombinant B. microplus Trypsin Inhibitor A) is a Kunitz-BPTI type inhibitor based on the native protein BmTI-A. BmTI-A was extracted from tick larvae and presented inhibitory activity against trypsin, human plasma kallikrein (HuPK), human neutrophil elastase (HNE) and human plasmin. rBmTI-A presented the same inhibitory activities of the BmTI-A and its thermostability has already been demonstrated. In emphysema induced by porcine pancreatic elastase (PPE) and by cigarette smoke animal models, the treatment using rBmTI-A showed a protective effect against the development of pulmonary emphysema and prevented the increase of inflammatory cells. In chronic allergic animal model, rBmTI-A treatment resulted in attenuated bronchial hyperresponsiveness, inflammation, remodeling. These are important physiological results in emphysema and lung inflammatory animal models with rBmTI-A treatment confirming its therapeutical potential.

Inflammasome-targeting natural compounds in inflammatory bowel disease: Mechanisms and therapeutic potential.

Inflammatory bowel disease (IBD), mainly including Crohn’s disease and ulcerative colitis, seriously affects human health and causes substantial social and economic burden. The pathogenesis of IBD is still not fully elucidated, whereas recent studies have demonstrated that its development is associated with the dysfunction of intestinal immune system. Accumulating evidence have proven that inflammasomes such as NLRP3 and NLRP6 play a prominent role in the pathogenesis of IBD. Thus, regulating the activation of inflammasomes have been considered to be a promising strategy in IBD treatment. A number of recent studies have provided evidence that blocking inflammasome related cytokine IL-1β can benefit a group of IBD patients with overactivation of NLRP3 inflammasome. However, therapies for targeting inflammasomes with high efficacy and safety are rare. Traditional medical practice provides numerous medical compounds that may have a role in treatment of various human diseases including IBD. Recent studies demonstrated that numerous medicinal herb derived compounds can efficiently prevent colon inflammation in animal models by targeting inflammasomes. Herein, we summarize the main findings of these studies focusing on the effects of traditional medicine derived compounds on colitis treatment and the underlying mechanisms in regulating the inflammasomes. On this basis, we provide a perspective for future studies regarding strategies to improve the efficacy, specificity and safety of available herbal compounds, and to discover new compounds using the emerging new technologies, which will improve our understanding about the roles and mechanisms of herbal compounds in the regulation of inflammasomes and treatment of IBD.

An ACE2-IgG4 Fc Fusion Protein Demonstrates Strong Binding to All Tested SARS-CoV-2 Variants and Reduced Lung Inflammation in Animal Models of SARS-CoV-2 and Influenza.

Background:The continued emergence of SARS-CoV-2 variants has caused concern that a constantly evolving virus will escape vaccines and antibody therapies. New approaches are needed.Methods:We created and manufactured an ACE2 extracellular domain (ECD) fragment Fc fusion drug candidate, G921, and engineered the compound for enhanced delivery of drug to peripheral tissues by minimizing the size of the ACE2 ECD and by incorporating an Fc domain to enhance transcytosis. G921 was assessed for binding, neutralization, in vivo anti-inflammatory effect, and pharmacokinetic profile.Results:G921 was expressed as an IgG4 Fc fusion protein presenting two ACE2 domains to ACE2 ligands while avoiding risk of infection via antibody-dependent enhancement. G921 strongly binds to the SARS-CoV-2 Wuhan-Hu-1 spike protein and demonstrates further diminished off rate to the spike protein from each of the currently identified variants of concern. G921 demonstrates ACE2 enzymatic activity comparable to positive control and binding to the neonatal Fc receptor (FcRn) without binding to low affinity Fc-gamma receptors (FcγRs). G921 is effective in a concentration-dependent manner in a focus reduction neutralization assay with EC50=16.3±4.2 µg/mL without cytotoxicity in Vero E6 cells when tested at 200 µg/mL in an MTS cell proliferation assay. G921 demonstrates statistically significant reduction of lung inflammation in relevant models of both SARS-CoV-2 and influenza. The pharmacokinetic profile demonstrated dose-dependent exposure with a multi-day half-life in monkeys and rats.Conclusion:G921 data are consistent with both antiviral and anti-inflammatory modes of action. G921 is a novel approach for the prevention and treatment of COVID-19 and possible other diseases characterized by deficiency of ACE2.

Lycium barbarum Glycopeptide prevents the development and progression of acute colitis by regulating the composition and diversity of the gut microbiota in mice.

In most cases, recurrent chronic colitis is caused by the recurrence of acute colitis after incomplete recovery and re-exposure to irritating factors, and the gut microbiome, which is the largest micro-ecosystem in the human body, plays a crucial role in the development of colitis. Plant polysaccharides have always been reported to have the ability for anti-inflammation, and they are closely related to the gut microbiome. Lycium barbarum Glycopeptide (LbGP), the most potent component obtained by further isolation and purification from Lycium barbarum fruit, has been shown to inhibit inflammation in animal models. However, its therapeutic efficacy in colitis and its mechanism in gut microbiota regulation have not been fully studied. In our study, the dextran sulfate sodium (DSS)-induced mouse model was used to dynamically evaluate the effect of LbGP in the treatment of acute colitis and the mechanism from the perspective of the gut microbiome through the 16S rDNA sequence. The results showed that LbGP treatment significantly alleviated acute colitis and improved the gut microbiome compared with that in the model group. Harmful bacteria, such as Lachnoclostridium spp. and Parabacteroides_distasonis, were inhibited and probiotics, such as Bacteroides_acidifaciens, Lactobacillus spp., Turicibacter spp., and Alistipes spp., were increased by LbGP treatment. Further, a Random Forest analysis with 10-fold cross-validation identified a family named Muribaculaceae representing colitis development and recovery upon LbGP treatment. In conclusion, our study demonstrated the capability of LbGP to prevent the development of acute colitis by regulating the composition and diversity of the gut microbiota and highlighted the dynamic process of gut microbiota with the colitis progression. Further, it provides evidence to develop LbGP as a functional food supplement and future drug acting on intestinal disease.

Mechanisms of action of anti-inflammatory proteins and peptides with anti-TNF-alpha activity and their effects on the intestinal barrier: A systematic review.

Several studies in animal models of intestinal inflammation have been performed with the aim of understanding the mechanisms of action of anti-inflammatory proteins and peptides that reduce TNF-α. In order to present the best targets, effects and strategies for the treatment of intestinal inflammation in experimental models, this systematic review (SR) aimed to answer the following question: what are the mechanisms of action of molecules with anti-TNF-α activity on the intestinal barrier? The SR protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, number CRD42019131862) and guided by the methodological procedures used for the elaboration of the SR. Articles that were part of the SR were selected considering the eligibility criteria according to the PICO (Population, Intervention, Comparison/Control and Outcomes) and were searched in the PubMed, Scopus, Web of Science, Excerpta Medica Database (EMBASE) and ScienceDirect databases. Twenty-five articles reporting studies in rats and mice were selected and the risk of bias was assessed using the tool from the SYstematic Review Center for Laboratory Animal Experimentation (SYRCLE). A descriptive synthesis of the results obtained was carried out. Based on the results, the anti-inflammatory molecules that reduced TNF-α acted mainly on the TNF-TNFR1/TNFR2 and TLR4/MD2 complex signaling pathways, and consequently on the NF-κB pathway. This improved the aspects of the inflammatory diseases studied. In addition, these mechanisms also improved the macroscopic, histological and permeability aspects in the intestine of the animals. These findings point to the potential of protein and peptide molecules that act on inflammatory pathways for medical applications with specific and promising strategic targets, aiming to improve inflammatory diseases that affect the intestine. This systematic review also highlights the need for more details during the methodological description of preclinical studies, since this was a limitation found.

Could Experimental Inflammation Provide Better Understanding of Migraines?

Migraines constitute a common neurological and headache disorder affecting around 15% of the world’s population. In addition to other mechanisms, neurogenic neuroinflammation has been proposed to play a part in migraine chronification, which includes peripheral and central sensitization. There is therefore considerable evidence suggesting that inflammation in the intracranial meninges could be a key element in addition to calcitonin gene-related peptide (CGRP), leading to sensitization of trigeminal meningeal nociceptors in migraines. There are several studies that have utilized this approach, with a strong focus on using inflammatory animal models. Data from these studies show that the inflammatory process involves sensitization of trigeminovascular afferent nerve terminals. Further, by applying a wide range of different pharmacological interventions, insight has been gained on the pathways involved. Importantly, we discuss how animal models should be used with care and that it is important to evaluate outcomes in the light of migraine pathology.

Extracellular vesicles modulate inflammatory signaling in chronically ischemic myocardium of swine with metabolic syndrome

ObjectiveExtracellular vesicle (EV) therapy has been shown to mitigate inflammation in animal models of acute myocardial ischemia/reperfusion. This study evaluates the effect of EV therapy on inflammatory signaling in a porcine model of chronic myocardial ischemia and metabolic syndrome. MethodsYorkshire swine were fed a high-cholesterol diet for 4 weeks to induce metabolic syndrome, then underwent placement of an ameroid constrictor to the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, pigs received intramyocardial injection of either saline (control) (n = 6) or EVs (n = 8). Five weeks later, pigs were put to death and left ventricular myocardial tissue in ischemic and nonischemic territories were harvested. Protein expression was measured with immunoblotting, and macrophage count was determined by immunofluorescent staining of cluster of differentiation 68. Data were statistically analyzed via Wilcoxon rank-sum test. ResultsEV treatment was associated with decreased expression of proinflammatory markers nuclear factor kappa B (P = .002), pro-interleukin (IL) 1ß (P = .020), and cluster of differentiation 11c (P = .001) in ischemic myocardium, and decreased expression of nuclear factor kappa B in nonischemic myocardium (P = .03) compared with control. EV treatment was associated with increased expression of anti-inflammatory markers IL-10 (P = .020) and cluster of differentiation 163 (P = .043) in ischemic myocardium compared with control. There were no significant differences in expression of IL-6, tumor necrosis factor alpha, arginase, HLA class II histocompatibility antigen DR alpha chain, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha, or phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha in ischemic myocardium or pro-IL1ß, IL-6, tumor necrosis factor alpha, IL-10, or nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha in nonischemic myocardium of EV-treated pigs compared with control. There were no differences in macrophage count in ischemic myocardium between EV-treated pigs and control. ConclusionsIn the setting of metabolic syndrome and chronic myocardial ischemia, intramyocardial EV therapy attenuates proinflammatory signaling.

Ceratonia siliqua leaves ethanol extracts exert anti-nociceptive and anti-inflammatory effects

BackgroundCeratonia siliqua L. (Leguminosae) has neuroprotective, mutagenic, hypotensive, anti-bacterial, hypoglycaemic, and anti-inflammatory effects through extracts from its leaves. Therefore, the aim of this study is to assess the anti-nociceptive activity of ethanol extracts of Ceratonia siliqua leaves. MethodsEthanol extract of Ceratonia siliqua leaves were studied using well-established animal models of inflammation and pain. A hot plate latency assay (55 °C) was used to assess the analgesic effect of 10, 31.6, 100, and 316 mg/kg doses of ethanol extracts in addition to paw licking time in early and late phase using a formalin-induced paw licking assay test. Paw oedema induction using carrageenan and cotton pellet granuloma assays were used to assess the anti-inflammatory effect of 10, 31.6, 100, and 316 mg/kg doses of ethanol extract. ResultsThe ethanol extract of Ceratonia siliqua leaves reduces paw licking time in early and late phase after formalin injection. The same effect was also observed when the hotplate test was performed. Ethanol extract of Ceratonia siliqua leaves caused dose dependent inhibition in paw oedema after the injection of carrageenan and cotton pellet granuloma in mice. These effects were not antagonized when opioid receptors were blocked by naloxone (5 mg/kg). The preliminary phytochemical analysis of the ethanol extract of Ceratonia siliqua leaves showed the presence of tannins, alkaloids, flavonoids and terpenoids. ConclusionThe present data indicate that ethanol extract of Ceratonia siliqua leaves might possess anti-inflammatory and anti-nociception properties and should be considered for further therapeutic research.

Progesterone Suppresses Uterine Contraction by Reducing Odontogenic Porphyromonas gingivalis Induced Chronic Inflammation in Mice.

Preterm birth is one of the most significant obstetric complications. Inflammation reportedly promotes uterine contraction and weakening of the fetal membrane, which induces preterm birth. Previous studies using animal models of lipopolysaccharide-induced acute inflammation have shown that progesterone (P4) promotes uterine quiescence. However, this effect is not fully understood in chronic inflammation. This study aimed to investigate the effects of P4 on uterine contractility and inflammation of the fetal membrane in mice infected with Porphyromonas gingivalis (P.g.), a major periodontal pathogen as a model of preterm birth caused by chronic inflammation. Mice were injected with 1 mg of P4 from day 15.5 to 17.5. P4 prolonged the mean gestation period of P.g mice from 18.3 to 20.4 days, and no reduction in the gestation period was observed. P4 treatment suppressed spontaneous uterine contractility and decreased oxytocin sensitivity. In addition, the expression of inflammatory cytokines in the fetal membrane was significantly reduced. Thus, P4 prevented preterm birth by suppressing enhanced uterine contractility induced by chronic inflammation in this model. This result describes the effects of P4 in a chronic inflammation model, which may lead to a better understanding of the efficacy of P4 in preventing preterm birth in humans.

Aging Relevant Metabolite Itaconate Inhibits Inflammatory Bone Loss.

Progressive bone loss during aging makes osteoporosis one of the most common and life impacting conditions in geriatric populations. The bone homeostasis is maintained through persistent remodeling mediated by bone-forming osteoblast and bone-resorbing osteoclast. Inflammaging, a condition characterized by increased pro-inflammatory markers in the blood and other tissues during aging, has been reported to be associated with skeletal stem/progenitor cell dysfunction, which will result in impaired bone formation. However, the role of age-related inflammation and metabolites in regulation of osteoclast remains largely unknown. In the present study, we observed dichotomous phenotypes of anti-inflammatory metabolite itaconate in responding to inflammaging. Itaconate is upregulated in macrophages during aging but has less reactivity in responding to RANKL stimulation in aged macrophages. We confirmed the inhibitory effect of itaconate in regulating osteoclast differentiation and activation, and further verified the rescue role of itaconate in lipopolysaccharides induced inflammatory bone loss animal model. Our findings revealed that itaconate is a crucial regulatory metabolite during inflammaging that inhibits osteoclast to maintain bone homeostasis.

Comparison of freshly cultured versus cryopreserved mesenchymal stem cells in animal models of inflammation: A pre-clinical systematic review.

Mesenchymal stem cells (MSCs) are multipotent cells that demonstrate therapeutic potential for the treatment of acute and chronic inflammatory-mediated conditions. Although controversial, some studies suggest that MSCs may lose their functionality with cryopreservation which could render them non-efficacious. Hence, we conducted a systematic review of comparative pre-clinical models of inflammation to determine if there are differences in in vivo measures of pre-clinical efficacy (primary outcomes) and in vitro potency (secondary outcomes) between freshly cultured and cryopreserved MSCs. A systematic search on OvidMEDLINE, EMBASE, BIOSIS, and Web of Science (until January 13, 2022) was conducted. The primary outcome included measures of in vivo pre-clinical efficacy; secondary outcomes included measures of in vitro MSC potency. Risk of bias was assessed by the SYRCLE 'Risk of Bias' assessment tool for pre-clinical studies. Eighteen studies were included. A total of 257 in vivo pre-clinical efficacy experiments represented 101 distinct outcome measures. Of these outcomes, 2.3% (6/257) were significantly different at the 0.05 level or less; 2 favoured freshly cultured and 4 favoured cryopreserved MSCs. A total of 68 in vitro experiments represented 32 different potency measures; 13% (9/68) of the experiments were significantly different at the 0.05 level or less, with seven experiments favouring freshly cultured MSC and two favouring cryopreserved MSCs. The majority of preclinical primary in vivo efficacy and secondary in vitro potency outcomes were not significantly different (p<0.05) between freshly cultured and cryopreserved MSCs. Our systematic summary of the current evidence base may provide MSC basic and clinical research scientists additional rationale for considering a cryopreserved MSC product in their pre-clinical studies and clinical trials as well as help identify research gaps and guide future related research. Ontario Institute for Regenerative Medicine.

In Situ Detection of Gastrointestinal Inflammatory Biomarkers Using Electrochemical Gas Sensors.

More than two decades ago it was discovered that nitric oxide (NO) concentrations in gas aspirated during colonoscopy were more than 100 times higher in patients diagnosed with Ulcerative Colitis (UC) than controls. While this provides a diagnostic opportunity, it has not been possible to perform in situ detection of NO via a non-invasive manner. This work presents the feasibility of in situ detection of NO by means of a capsule-like electrochemical gas sensor. Our in vivo results in a large animal model of intestinal inflammation show that NO can be directly detected at the site of inflammation and that it quickly dissipates to surrounding tissues, demonstrating the importance of in situ detection.

Impact of the Exposome on the Epigenome in Inflammatory Bowel Disease Patients and Animal Models.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn’s disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits, vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated.

Cell-Specific Immune Regulation by Glucocorticoids in Murine Models of Infection and Inflammation.

Glucocorticoids (GC) are highly potent negative regulators of immune and inflammatory responses. Effects of GC are primarily mediated by the glucocorticoid receptor (GR) which is expressed by all cell types of the immune system. It is, therefore, difficult to elucidate how endogenous GC mediate their effects on immune responses that involve multiple cellular interactions between various immune cell subsets. This review focuses on endogenous GC targeting specific cells of the immune system in various animal models of infection and inflammation. Without the timed release of these hormones, animals infected with various microbes or challenged in inflammatory disease models succumb as a consequence of overshooting immune and inflammatory responses. A clearer picture is emerging that endogenous GC thereby act in a cell-specific and disease model-dependent manner, justifying the need to develop techniques that target GC to individual immune cell types for improved clinical application.

Development of a nanotechnological hydrogel containing desonide nanocapsules in association with acai oil: design and in vivo evaluation

Nanotechnological products have been used as strategies to optimize the therapy and minimize the side effects of topical corticoids. The objective of this study was to develop hydrogels by the addition of sclerotium gum to the suspensions of desonide-loaded açai oil-based nanocapsules and to study their biological effect using an animal model of acute skin inflammation. The hydrogels presented a pH compatible with topical application (4.4 to 5.0), nanometric mean diameter (131 to 165 nm), pseudoplastic behavior, and stability under room conditions during 30 days. The in vitro skin permeation/penetration study demonstrated that a higher amount of desonide (p < 0.05) was retained in the epidermis from the nanotechnological-hydrogels (0.33 to 0.36 µg.cm2) in comparison to the commercial gel cream (0.16 µg.cm2). In the dermis, the nanostructured hydrogels promoted a lower DES retention compared to the non-nanostructured formulations (p < 0.05). This result may indicate a smaller amount of drug reaching the bloodstream and, thus, fewer side effects can be expected. Concerning the anti-inflammatory effect, the developed hydrogels reduced both ear edema and inflammatory cell infiltration, showing an effect comparable to the commercially available formulation, which presents twice the drug concentration. The hydrogels developed may be considered a promising approach to treat dermatological disorders.