Levels Of Cytokines IL-6 Research Articles

Anti-inflammatory effect of hydrogen sulfide donor sodium-sulfide in an experimental mouse model of contact hypersensitivity

Background: Hydrogen sulfide (H2S), synthesized by most immune cells, has been shown to exert anti-inflammatory and antipruritic effects. The effect of H2S on allergic contact dermatitis (ACD), an inflammatory skin disease that negatively affects the quality of life, is unknown. Objectives: We planned to investigate the antipruritic and anti-inflammatory effects of the H2S donor sodium sulfide (Na2S) in the experimental mouse model of contact hypersensitivity (CHS), which is widely used for ACD research. Methods: CHS was created in Balb/c mice using 1-fluoro-2, 4-dinitrobenzene. Na2S was administered systemically (0.2-2-20 mg/kg/i.p.) and locally (1-3-10 nmol/both ear/i.d.) at 3 h and 25 h after the challenge. Ear thickness and the number of scratches were determined at 24 h and 48 h following the challenge. Ear tissue and serum interferon-gamma, interleukin (IL)-2, IL-4, and IL-5 cytokine levels were evaluated by enzyme-linked immunosorbent assay (ELISA). H and E staining was performed for histopathological studies. CD4+ and CD8+ T cells located in the skin were examined by immunohistochemical staining. Results: Locally (1-3-10 nmol/ear/i.d., P < 0.001, P < 0.0001, P < 0.0001, respectively) and systemically (2–20 mg/kg/i.p., P < 0.01, P < 0.0001, respectively), Na2S administration decreased ear thickness dose dependently. Local (1-3-10 nmol/ear/i.d.) Na2S treatment decreased serum IL-2 levels (P < 0.01, P < 0.05, and P < 0.01, respectively). Na2S administered locally (3–10 nmol/ear/i.d., P < 0.05) and systemically (20 mg/kg/i. p., P < 0.05) decreased the number of CD4+ T lymphocytes. Conclusion: Locally and systemically administered Na2S reduces ear thickness, which is one of the symptoms of CHS, probably by preventing CD4+ T lymphocyte infiltration and proliferation and decreasing IL-2 synthesis.

Correlations of interleukin levels with the severity of SARS-CoV-2 coronavirus infection

A new coronavirus infection caused by the SARS-CoV-2 virus is characterized by a systemic hyperinflammatory response with a pronounced increase in the content of pro-inflammatory cytokines. Materials and methods . The study was conducted on the basis of the Samara Regional Children's Infectious Diseases Hospital from 2021 to 2022. 40 patients with moderate (n = 20, group I) and severe forms (n = 20, group II) COVID-19 were studied, the comparison group consisted of patients with viral pneumonia of another etiology (n = 35, group III). Results . The infectious agent SARS-CoV-2 induces high levels of cytokines IL-6 (p < 0.005), IL-8 (p < 0.05) and a slight increase in TNF-α (p < 0.05). IL-8 was significantly associated with disease duration (p < 0.01). We assume that the value of this interleukin will increase in the post-COVID period. Conclusions . Changes in IL-6 and IL-8 levels in patients with COVID-19, along with clinical features, are important biomarkers for predicting the severity and duration of the disease.

Staphylococcal enterotoxin B as DNA vaccine against breast cancer in a murine model.

Recently, many efforts have been made to treat cancer using recombinant bacterial toxins and this strategy has been used in clinical trials of various cancers. Therapeutic DNA cancer vaccines are now considered as a promising strategy to activate the immune system against cancer. Cancer vaccines could induce specific and long-lasting immune responses against tumors. This study aimed to evaluate the antitumor potency of the SEB DNA vaccine as a new antitumor candidate against breast tumors in vivo. To determine the effect of the SEB construct on inhibiting tumor cell growth in vivo, the synthetic SEB gene, subsequent codon optimization, and embedding the cleavage sites were sub-cloned to an expression vector. Then, SEB construct, SEB, and PBS were injected into the mice. After being vaccinated, 4T1 cancer cells were injected subcutaneously into the right flank of mice. Then, the cytokine levels of IL-4 and IFN-γ were estimated by the ELISA method to evaluate the antitumor activity. The spleen lymphocyte proliferation, tumor size, and survival time were assessed. The concentration of IFN-γ in the SEB-Vac group showed a significant increase compared to other groups. The production of IL-4 in the group that received the DNA vaccine did not change significantly compared to the control group. The lymphocyte proliferation increased significantly in the mice group that received SEB construct than PBS control group (p < 0.001). While there was a meaningful decrease in tumor size (p < 0.001), a significant increase in tumor tissue necrosis (p < 0.01) and also in survival time of the animal model receiving the recombinant construct was observed. The designed SEB gene construct can be a new model vaccine for breast cancer because it effectively induces necrosis and produces specific immune responses. This structure does not hurt normal cells and is a safer treatment than chemotherapy and radiation therapy. Its slow and long-term release gently stimulates the immune system and cellular memory. It could be applied as a new model for inducing apoptosis and antitumor immunity to treat cancer.

Escherichia coli-induced inflammatory responses are temperature-dependent in human whole blood ex vivo

Systemic inflammatory conditions are often associated with hypothermia or hyperthermia. Therapeutic hypothermia is used in post-cardiac arrest and some other acute diseases. There is a need for more knowledge concerning the effect of various temperatures on the acute inflammatory response. The complement system plays a crucial role in initiating the inflammatory response. We hypothesized that temperatures above and below the physiologic 37 °C affect complement activation and cytokine production ex vivo. Lepirudin-anticoagulated human whole blood from 10 healthy donors was incubated in the presence or absence of Escherichia coli at different temperatures (4 °C, 12 °C, 20 °C, 33 °C, 37 °C, 39 °C, and 41 °C). Complement activation was assessed by the terminal C5b-9 complement complex (TCC) and the alternative convertase C3bBbP using ELISA. Cytokines were measured using a 27-plex assay. Granulocyte and monocyte activation was evaluated by CD11b surface expression using flow cytometry. A consistent increase in complement activation was observed with rising temperature, reaching a maximum at 41 °C, both in the absence (C3bBbP p < 0.05) and presence (C3bBbP p < 0.05 and TCC p < 0.05) of E. coli. Temperature alone did not affect cytokine production, whereas incubation with E. coli significantly increased cytokine levels of IL-1β, IL-2, IL-6, IL-8, IFN-γ, and TNF at temperatures > 20 °C. Maximum increase occurred at 39 °C. However, a consistent decrease was observed at 41 °C, significant for IL-1β (p = 0.003). Granulocyte CD11b displayed the same temperature-dependent pattern as cytokines, with a corresponding increase in endothelial cell apoptosis and necrosis. Thus, blood temperature differentially determines the degree of complement activation and cytokine release.

Effect of anti-adhesion agents on cytokine profile in an experimental model of postoperative intra-abdominal adhesions

Many attempts have been made to prevent peritoneal adhesions using anti-adhesion agents, barriers and other therapeutic approaches, but their efficacy has not been widely accepted. Purpose – to determine the effects of mezogel, a mixture of metronidazole, dextran, and contrykal enriched with oxygen based on the pro- and anti-inflammatory cytokine concentration in rats with simulated postoperative peritoneal adhesions. Materials and methods. A total of 90 outbred white rats, divided into three groups of 30 animals each, underwent laparotomy and mechanical injury of the small bowel wall until a drop of blood appeared. After mechanical injury of the small bowel wall, the abdominal wound in group 1 animals (control) was closed with a layered suture technique; group 2 animals (comparison) were administered one mL of mezogel into the abdominal cavity before layer-by-layer suturing; group 3 animals (experimental) were introduced one mL of a specially prepared mixture of metronidazole, dextran, and contrykal (in a ratio of 1:1:0.1, respectively) enriched with oxygen into the abdominal cavity before the laparotomy wound was closed. Each surgical intervention lasted 15–20 minutes. On days 5, 10 and 21 of the experiment interleukin (IL) 4, IL-6, IL-10 and tumour necrosis factor alpha (TNF-α) were determined in the blood by enzyme immunoassay using corresponding test kits manufactured by Bender Medsystems (Austria). Results. The levels of the anti-inflammatory cytokines IL-4 and IL-10 increased dynamically in groups 2 and 3, while group 1 showed their decrease. The proinflammatory cytokine IL-6 and TNF-α concentration decreased in the experimental and comparison groups during the study period. On day 5 in groups 2 and 3, compared to group 1, the IL-6 concentration was reduced by 28.4% (p=0.029) and 41.0% (p=0.006), respectively. Group 3 animals had a 17.6% (p=0.043) lower IL-6 level compared to group 2 animals. On days 10 and 21 a dynamic decrease in IL-6 was observed in the animals of groups 2 and 3. Group 3 animals had the lowest TNF-α, 41.9 % (p=0.001) lower than in group 1, and 31.7 % (p=0.118) lower than in group 2. There were significant strong relationships detected between IL-10 and IL-6 in all groups on day 5 of the study. Conclusions. The administration of anti-adhesion agents, mezogel and an oxygen-enriched mixture of metronidazole, dextran, and contrykal, inhibits inflammation, which is expressed as a decrease in the concentrations of IL-6 and TNF-α. These agents lead to a negative interaction of anti-inflammatory cytokines with pro-inflammatory cytokines, in particular IL-4 with IL-6 and IL-10 with IL-6, indicating a greater prophylactic effect. The experiments with laboratory animals were provided in accordance with all bioethical norms and guidelines. No conflict of interests was declared by the authors.

Chimonanthus salicifolius extract alleviates DSS-induced colitis and regulates gut microbiota in mice.

Ulcerative colitis is a chronic and recurrent gastrointestinal intestinal disease accompanied by inflammatory disorders, immunologic inadequacy, and intestinal flora dysbiosis, and current therapeutic pharmaceuticals have limited side effects. In this study, we revealed the extraction method of Chimonanthus salicifolius, analyzed the main component, compared the effect of its extract, Lactobacillus, and conventional drugs with different properties on DSS (dextran sodium sulfate)-induced colitis, and indicated extract regulatory properties of inestinal flora. A colitis model was established on experimental design, and BALB/c mice (male, 7 weeks old) were randomly assigned to five groups (n=10): control, DSS model, Chimonanthus salicifolius extract (CSE), Lactobacillus rhamnosus GG (LGG), and 5-aminosalicylic acid (5-ASA) groups. The three treatments could alleviate the symptoms and remit inflammation induced by DSS, in which CSE and LGG groups could both decrease the proinflammatory cytokine IL-6, IL-8, and TNF-α levels and increase anti-inflammatory cytokines IL-10 and TGF-β. The CSE intervention significantly promoted the higher production of butyric acid than LGG and 5-ASA groups (p < .05) after DSS challenge. Analysis of intestinal flora showed that CSE administration remarkably decreased the relative abundance of pathogenic bacteria Heliobacteriaceae and Peptococcaceae and exhibited higher abundance of Lactobacillaceae and Bifidobacterium than LGG in intestinal tract of mice (p < .05). These findings indicated that Chimonanthus salicifolius extract may have been beneficial for preventing and treating colitis.

Microbiome and Th cytokines association in chronic rhinosinusitis with or without nasal polyp.

Chronic rhinosinusitis (CRS), a common disease in otorhinolaryngology, seriously affects the life quality of patients. The existing therapy has certain limitations, and it is very urgent to deeply explore the pathogenesis and classification of CRS. Microbiome and inflammation are considered the causes of CRS, but the precise roles and the associations between these two factors in the pathogenesis of CRS remain controversial. Secretions were collected from the middle nasal canal, maxillary sinus and ethmoid sinus in CRS patients, then subjected to 16 S rRNA gene sequencing to profile microbiota community. Operational Taxonomic Units clustering and species annotation were adopted to obtain species diversity, prevalence rate and average relative abundance. Comparisons were performed at the level of microbial species and genus between CRS and control using NMDS, Anosim and MetaStat analysis. Th1 cytokines and Th2 cytokines were detected by ELISA. Spearman analysis were adopted to probe into the correlation between Th cytokines and microbial species in CRS. Thirty-seven patients were enrolled, among them 22 with CRS and 15 were controls. The most abundant genera were Corynebacterium and Staphylococcus no matter in CRS patients or control. Corynebacterium propinquum was significant decreased in CRS patients no matter with nasal polyp or not. The abundances of Prevotella birria and Carnobacterium maltaromaticum were significantly different between CRSsNP and CRSwNP group. The levels of cytokines IL-2, TNF-α, IFN-ɣ, IL-4, IL-6, IL-10 were all increased in CRS patients. The cytokines levels were associated with specific microbial species in nasal tissue. The changes of species richness and complexity in nasal microbiome were obvious in CRS patients with nasal polyps or not. The different cytokines levels and microbiome between CRS patients without nasal polyps and patients with nasal polyps suggest heterogeneity in pathogenesis of chronic rhinosinusitis. Distinct microbiota and different cytokines were strongly linked in CRS. NA.

Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis.

Persistent post-breeding induced endometritis (PPBIE) is considered a major cause of subfertility in mares. It consists of persistent or delayed uterine inflammation in susceptible mares. There are many options for the treatment of PPBIE, but in this study, a novel approach aimed at preventing the onset of PPBIE was investigated. Stallion semen was supplemented with extracellular vesicles derived from amniotic mesenchymal stromal cells (AMSC-EVs) at the time of insemination to prevent or limit the development of PPBIE. Before use in mares, a dose-response curve was produced to evaluate the effect of AMSC-EVs on spermatozoa, and an optimal concentration of 400 × 106 EVs with 10 × 106 spermatozoa/mL was identified. At this concentration, sperm mobility parameters were not negatively affected. Sixteen susceptible mares were enrolled and inseminated with semen (n = 8; control group) or with semen supplemented with EVs (n = 8; EV group). The supplementation of AMSC-EVs to semen resulted in a reduction in polymorphonuclear neutrophil (PMN) infiltration as well as intrauterine fluid accumulation (IUF; p < 0.05). There was a significant reduction in intrauterine cytokine levels (p < 0.05) for TNF-α and IL-6 and an increase in anti-inflammatory IL-10 in mares in the EV group, suggesting successful modulation of the post-insemination inflammatory response. This procedure may be useful for mares susceptible to PPBIE.

Adenosine 2A receptor contributes to the facilitation of post-infectious irritable bowel syndrome by γδ T cells via the PKA/CREB/NF-κB signaling pathway.

Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome (PI-IBS). γδ T cells play a crucial role in innate and adaptive immunity. Adenosine receptors expressed on the surface of γδ T cells participate in intestinal inflammation and immunity regulation. To investigate the role of γδ T cell regulated by adenosine 2A receptor (A2AR) in PI-IBS. The PI-IBS mouse model has been established with Trichinella spiralis (T. spiralis) infection. The intestinal A2AR and A2AR in γδ T cells were detected by immunohistochemistry, and the inflammatory cytokines were measured by western blot. The role of A2AR on the isolated γδ T cells, including proliferation, apoptosis, and cytokine production, were evaluated in vitro. Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction (RT-PCR). The animals were administered with A2AR agonist, or A2AR antagonist. Besides, γδ T cells were also injected back into the animals, and the parameters described above were examined, as well as the clinical features. Furthermore, the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR. PI-IBS mice exhibited elevated ATP content and A2AR expression (P < 0.05), and suppression of A2AR enhanced PI-IBS clinical characteristics, indicated by the abdominal withdrawal reflex and colon transportation test. PI-IBS was associated with an increase in intestinal T cells, and cytokine levels of interleukin-1 (IL-1), IL-6, IL-17A, and interferon-α (IFN-α). Also, γδ T cells expressed A2AR in vitro and generated IL-1, IL-6, IL-17A, and IFN-α, which can be controlled by A2AR agonist and antagonist. Mechanistic studies demonstrated that the A2AR antagonist improved the function of γδ T cells through the PKA/CREB/NF-κB signaling pathway. Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function of γδ T cells via the PKA/CREB/NF-κB signaling pathway.

Omega-3 polyunsaturated fatty acids alleviate early brain injury after traumatic brain injury by inhibiting neuroinflammation and necroptosis.

Presently, traumatic brain injury (TBI) is a leading contributor to disability and mortality that places a considerable financial burden on countries all over the world. Docosahexaenoic acid and eicosapentaenoic acid are two kinds of omega-3 polyunsaturated fatty acids (ω-3 PUFA), both of which have been shown to have beneficial biologically active anti-inflammatory and antioxidant effects. However, the neuroprotective effect of ω-3 PUFA in TBI has not been proven, and its probable mechanism remains obscure. We suppose that ω-3 PUFA can alleviate early brain injury (EBI) via regulating necroptosis and neuroinflammation after TBI. This research intended to examine the neuroprotective effect of ω-3 and its possible molecular pathways in a C57BL/6 mice model of EBI caused by TBI. Cognitive function was assessed by measuring the neuronal necroptosis, neuroinflammatory cytokine levels, brain water content, and neurological score. The findings demonstrate that administration of ω-3 remarkably elevated neurological scores, alleviated cerebral edema, and reduced inflammatory cytokine levels of NF-κB, interleukin-1β (IL-1β), IL-6, and TNF-α, illustrating that ω-3 PUFA attenuated neuroinflammation, necroptosis, and neuronal cell death following TBI. The PPARγ/NF-κB signaling pathway is partially responsible for the neuroprotective activity of ω-3. Collectively, our findings illustrate that ω-3 can alleviate EBI after TBI against neuroinflammation and necroptosis.

BjussuLAAO-II, an l-amino acid oxidase from Bothrops jararacussu snake venom, impairs Toxoplasma gondii infection in human trophoblast cells and villous explants from the third trimester of pregnancy

One-third of the world's population is estimated to be affected by toxoplasmosis. Pregnancy-related Toxoplasma gondii infection can cause vertical transmission, infect the fetus, and cause miscarriage, stillbirth, and fetal death. The current study showed that both human trophoblast cells (BeWo lineage) and human explant villous were resistant to T. gondii infection after incubation with BjussuLAAO-II, an l-amino acid oxidase isolated from Bothrops jararacussu. Almost 90% of the parasite’s ability to proliferate in BeWo cells was decreased by the toxin at 1.56 μg/mL and showed an irreversible anti-T. gondii effect. Also, BjussuLAAO-II impaired the key events of adhesion and invasion of T. gondii tachyzoites in BeWo cells. BjussuLAAO-II antiparasitic properties were associated with the intracellular production of reactive oxygen species and hydrogen peroxide, since the presence of catalase restored the parasite’s growth and invasion. In addition, T. gondii growth in human villous explants was decreased to approximately 51% by the toxin treatment at 12.5 μg/mL. Furthermore, BjussuLAAO-II treatment altered IL-6, IL-8, IL-10 and MIF cytokines levels, assuming a pro-inflammatory profile in the control of T. gondii infection. This study contributes to the potential use of a snake venom l-amino acid oxidase for the development of agents against congenital toxoplasmosis and the discovery of new targets in parasites and host cells.

Differential therapeutic activity of a cargo-free nanoparticle in eosinophilic and neutrophilic asthma mouse models

Asthma is a complex, heterogeneous chronic airway inflammatory disorder, which can be simply categorized into eosinophilic and neutrophilic asthma. Although most patients with eosinophilic asthma can be well managed by glucocorticoid therapy, the patients with neutrophilic asthma have poor responses to corticosteroids, and there are no effective clinical treatments for neutrophilic asthma. Studies have shown that M1 macrophages are associated with the pathophysiology of neutrophilic asthma. We previously developed a novel cargo-free anti-inflammatory nanoparticle (P12), which can promote macrophage polarization from M1 to the M2 phenotype. Herein, we aim to explore the therapeutic activities of P12 in eosinophilic asthma and neutrophilic asthma and the mechanisms of action behind. Using the mouse models of eosinophilic and neutrophilic asthma, we found that the intratracheally administered P12 reduced the airway resistance in both models. However, P12 had higher therapeutic effects in neutrophilic asthma than in eosinophilic asthma, particularly on the pathological score, the serum IgE level, the BAL differential cell count and the proinflammatory cytokine IL-17A and IL-6 levels. Mechanistically, P12 facilitated M2 macrophage polarization by inhibiting transcription factors NF-κB and STAT1 activation and up-regulating STAT3 signaling in vitro; in the asthma models, P12 promoted M2 polarization of both alveolar and interstitial macrophages, and reduced the downstream Th17/Treg ratio in mice with neutrophilic asthma. Finally, P12 showed a good biosafety profile in healthy mice, facilitating the clinical translation of P12. This study provides a new strategy and lung macrophage targeted nanotherapeutics for the treatment of neutrophilic asthma.

Examining Brain Structural Connectivity in Early-life Interpersonal Stress

IntroductionEarly-life interpersonal stress, particularly childhood maltreatment (CM), is associated with social cognition deficits as well as neurobiological abnormalities including alterations in brain structure and function and heightened inflammation. However, few studies have investigated whether peer victimisation (PV) has similar effects.ObjectivesThis study first examines the associations between white matter tract abnormalities and childhood interpersonal stress from carers (CM) and peers (PV). Next, it explores how the observed tract alterations are in terms related to cytokine IL-6 level and theory of mind (ToM) performance in the CM and PV groups.MethodsData were collected from 107 age-and gender-matched youths (34 CM, 35 PV and 38 controls). Tractography and whole-brain tract-based spatial statistics (TBSS) analyses were conducted.ResultsTractography showed that both CM and PV groups had smaller right inferior longitudinal fasciculus (ILF) tract volume than controls, which was furthermore associated with longer maltreatment duration within the CM group. At the microstructural level, the CM group had higher fractional anisotropy (FA) of bilateral anterior thalamic radiation (ATR) than both PV and control groups, which were associated with enhanced affective ToM performance in maltreated individuals only. Reduced left ATR FA, however, was associated with greater emotional and behavioural difficulties in the PV group. Using TBSS, the CM group had higher FA than both PV and control groups in predominantly right-hemispheric limbic tracts (UF, ATR, ILF, cingulum bundle and inferior fronto-occipital fasciculus), corpus callosum and corona radiata, which were furthermore associated with heightened cytokine IL-6 level within the CM group.ConclusionsEarly-life interpersonal stress, particularly from carers, is associated with widespread alterations of neural pathways connecting the frontal, temporal and occipital cortices involved in cognitive and affective control. The adverse caregiving experience may conceivably contribute to enhanced mental-state decoding but there exists a hidden cost of heightened inflammation in these seemingly healthy maltreated youths. Our findings thus underscore the need to further examine the mental and physical well-being of healthy individuals exposed to early-life stress as they may still be vulnerable to psychopathology later on.Disclosure of InterestNone Declared

Repurposing Astragalus Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that Astragalus polysaccharide (PG2), a mixture of polysaccharides purified from Astragalus membranaceus, could effectively reverse COVID-19 signature genes. Further biological assays revealed that PG2 could prevent the fusion of BHK21-expressing wild-type (WT) viral spike (S) protein and Calu-3-expressing ACE2. Additionally, it specifically prevents the binding of recombinant viral S of WT, alpha, and beta strains to ACE2 receptor in our non-cell-based system. In addition, PG2 enhances let-7a, miR-146a, and miR-148b expression levels in the lung epithelial cells. These findings speculate that PG2 has the potential to reduce viral replication in lung and cytokine storm via these PG2-induced miRNAs. Furthermore, macrophage activation is one of the primary issues leading to the complicated condition of COVID-19 patients, and our results revealed that PG2 could regulate the activation of macrophages by promoting the polarization of THP-1-derived macrophages into an anti-inflammatory phenotype. In this study, PG2 stimulated M2 macrophage activation and increased the expression levels of anti-inflammatory cytokines IL-10 and IL-1RN. Additionally, PG2 was recently used to treat patients with severe COVID-19 symptoms by reducing the neutrophil-to-lymphocyte ratio (NLR). Therefore, our data suggest that PG2, a repurposed drug, possesses the potential to prevent WT SARS-CoV-2 S-mediated syncytia formation with the host cells; it also inhibits the binding of S proteins of WT, alpha, and beta strains to the recombinant ACE2 and halts severe COVID-19 development by regulating the polarization of macrophages to M2 cells.

Depressive-like Behavior Is Accompanied by Prefrontal Cortical Innate Immune Fatigue and Dendritic Spine Losses after HIV-1 Tat and Morphine Exposure.

Opioid use disorder (OUD) and HIV are comorbid epidemics that can increase depression. HIV and the viral protein Tat can directly induce neuronal injury within reward and emotionality brain circuitry, including the prefrontal cortex (PFC). Such damage involves both excitotoxic mechanisms and more indirect pathways through neuroinflammation, both of which can be worsened by opioid co-exposure. To assess whether excitotoxicity and/or neuroinflammation might drive depressive behaviors in persons infected with HIV (PWH) and those who use opioids, male mice were exposed to HIV-1 Tat for eight weeks, given escalating doses of morphine during the last two weeks, and assessed for depressive-like behavior. Tat expression decreased sucrose consumption and adaptability, whereas morphine administration increased chow consumption and exacerbated Tat-induced decreases in nesting and burrowing-activities associated with well-being. Across all treatment groups, depressive-like behavior correlated with increased proinflammatory cytokines in the PFC. Nevertheless, supporting the theory that innate immune responses adapt to chronic Tat exposure, most proinflammatory cytokines were unaffected by Tat or morphine. Further, Tat increased PFC levels of the anti-inflammatory cytokine IL-10, which were exacerbated by morphine administration. Tat, but not morphine, decreased dendritic spine density on layer V pyramidal neurons in the anterior cingulate. Together, our findings suggest that HIV-1 Tat and morphine differentially induce depressive-like behaviors associated with increased neuroinflammation, synaptic losses, and immune fatigue within the PFC.

Protective Effect of Lactiplantibacillus plantarum subsp. plantarum SC-5 on Dextran Sulfate Sodium-Induced Colitis in Mice.

Inflammatory bowel disease (IBD) is a specific immune-associated intestinal disease. At present, the conventional treatment for patients is not ideal. Probiotics are widely used in the treatment of IBD patients due to their ability to restore the function of the intestinal mucosal barrier effectively and safely. Lactiplantibacillus plantarum subsp. plantarum is a kind of probiotic that exists in the intestines of hosts and is considered to have good probiotic properties. In this study, we evaluated the therapeutic effect of Lactiplantibacillus plantarum subsp. plantarum SC-5 (SC-5) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. We estimated the effect of SC-5 on the clinical symptoms of mice through a body weight change, colon length, and DAI score. The inhibitory effects of SC-5 on the levels of cytokine IL-1β, IL-6, and TNF-α were determined by ELISA. The protein expression levels of NF-κB, MAPK signaling pathway, and the tight junction proteins occludin, claudin-3, and ZO-1 were verified using Western Blot and immunofluorescence. 16S rRNA was used to verify the modulatory effect of SC-5 on the structure of intestinal microbiota in DSS-induced colitis mice. The results showed that SC-5 could alleviate the clinical symptoms of DSS-induced colitis mice, and significantly reduce the expression of pro-inflammatory cytokines in the colon tissue. It also attenuated the inflammatory response by inhibiting the protein expression of NF-κB and MAPK signaling pathways. SC-5 improved the integrity of the intestinal mucosal barrier by strengthening tight junction proteins. In addition, 16S rRNA sequencing demonstrated that SC-5 was effective in restoring intestinal flora balance, as well as in increasing the relative abundance and diversity of beneficial microbiota. These results indicated that SC-5 has the potential to be developed as a new probiotic candidate that prevents or alleviates IBD.

The protective role of vitamin C on intestinal damage induced by high-dose glycinin in juvenile Rhynchocypris lagowskii Dybowski

This study was to evaluate the mitigative effects of vitamin C (VC) on growth inhibition and intestinal damage induced by glycinin in juvenile Rhynchocypris lagowskii Dybowski. 270 healthy juvenile Rhynchocypris lagowskii Dybowski (4.65 ± 0.04 g) were randomly divided into 3 treatments, and fed with control diet, 80 g/kg glycinin diet and 80 g/kg glycinin+200 mg/kg VC diet respectively for 8 weeks. The results showed that glycinin significantly decreased the weight gain rate, specific growth rate, protein efficiency rate, feed efficiency rate and feeding rate of fish compared with the control group (P < 0.05), while VC supplementation improved the growth performance and feed utilization efficiency, and reached a level similar to the control group. Similarly, VC significantly increased the crude protein content of muscle and whole-body, and hepatopancreas and intestinal protease activities of fish fed with glycinin diet (P < 0.05). The distal intestine of fish in glycinin group showed typical damage characteristics, including breakage and atrophy of intestinal mucosal fold, and increased intestinal mucosal permeability. However, fish fed the glycinin + VC diet showed an unimpaired normal intestinal morphology. Usefully, VC supplementation could also restore impaired immune function and antioxidant capacity. VC down-regulated the mRNA levels of pro-inflammatory cytokines TNF‐α and IL-1β, and up-regulated the mRNA levels of anti-inflammatory cytokines IL-10 and TGF-β in the distal intestine of fish fed with glycinin. Furthermore, glycinin exposure could reduce the mRNA levels of HO-1, CAT and GPx by inhibiting the activation of Nrf2-Keap1 signaling pathway, while VC supplementation reversed this phenomenon and maintained the homeostasis of antioxidant defense system. Concluded, glycinin causes growth inhibition, digestive dysfunction and intestinal damage of Rhynchocypris lagowskii Dybowski, while sufficient VC intake is beneficial for fish to resist the adverse effects of glycinin.

Investigating the correlation of the NF-κB and FoxP3 gene expression with the plasma levels of pro- and anti-inflammatory cytokines in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disease. Cytokines regulate a wide range of inflammatory processes involved in RA pathogenesis. Anti-inflammatory cytokines (i.e., TGF-β and lL-10) and pro-inflammatory cytokines, like IL-6, were found to be potentially implicated in RA pathogenesis. Besides, NF-κB and FoxP3 are critical transcription factors regulating the inflammatory events occurring in RA patients. This study intends to assess the plasma levels of IL-6, IL-10, and TGF-β1 cytokines, as well as the expression of NF-κB and FoxP3 genes in RA patients, compared to the healthy controls. Peripheral blood was collected from 50 RA patients (25 new case and 25 under-treatment) and 25 age- and gender-matched healthy subjects. The disease activity was determined using the DAS-28 and ESR criteria. Also, plasma levels of TGF-β1, lL-10, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) technique, and the gene expression of NF-κB and FoxP3 was evaluated using the real-time PCR method. Our results showed a significant up-regulation of Rel-A and NF-κB1, and also a down-regulation of FoxP3 gene expression in under-treatment RA patients compared to the controls (P=0.031, P=0.014, and P=0.011, respectively). Moreover, there was a significant reduction of Rel-A and FoxP3 in the under-treatment RA patients compared to new case RA patients (P=0.005 and P=0.015, respectively). Also, plasma levels of TGF-β1 were significantly increased in both the new case and under-treatment RA patients relative to controls (P<0.001). In conclusion, classical NF-κB (P65/P50) and FoxP3 may have significant pro- and anti-inflammatory roles in RA pathogenesis, respectively. Key Point •NF-κB (P65/P50) has a contribution to the early phase of RA.

The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line

The ketogenic diet (KD), a diet high in fat and protein but low in carbohydrates, is gaining much interest due to its positive effects, especially in neurodegenerative diseases. Beta-hydroxybutyrate (BHB), the major ketone body produced during the carbohydrate deprivation that occurs in KD, is assumed to have neuroprotective effects, although the molecular mechanisms responsible for these effects are still unclear. Microglial cell activation plays a key role in the development of neurodegenerative diseases, resulting in the production of several proinflammatory secondary metabolites. The following study aimed to investigate the mechanisms by which BHB determines the activation processes of BV2 microglial cells, such as polarization, cell migration and expression of pro- and anti-inflammatory cytokines, in the absence or in the presence of lipopolysaccharide (LPS) as a proinflammatory stimulus. The results showed that BHB has a neuroprotective effect in BV2 cells, inducing both microglial polarization towards an M2 anti-inflammatory phenotype and reducing migratory capacity following LPS stimulation. Furthermore, BHB significantly reduced expression levels of the proinflammatory cytokine IL-17 and increased levels of the anti-inflammatory cytokine IL-10. From this study, it can be concluded that BHB, and consequently the KD, has a fundamental role in neuroprotection and prevention in neurodegenerative diseases, presenting new therapeutic targets.

Sub-group analysis of inflammatory cytokines IL-1 and IL-6 in association with lipid profiles of coronary artery disease patients

IntroductionAlthough possible effects of lipid parameters, and several important genetic factors, and cytokines on the development of coronary artery disease (CAD) have been demonstrated, there is still debate about how the lipid profile affects the sub-group of patients in a specific population. This study aimed to evaluate age- and gender-based effect of lipid profile in correlation with their IL-1 and IL-6 cytokine levels in South Indian population. MethodsAngiographically confirmed 150 CAD patients' with or without hypertension and 150 healthy control individuals of both the genders between 18 and 70 years of age were enrolled. Quantitative estimation of IL-1 and IL-6 protein in each serum sample was evaluated using ELISA. The plasma concentrations of cholesterol, HDL, LDL, VLDL and triglycerides were determined using different biochemical tests. Correlation was established between cytokines and lipid profile of patients in different sub-groups using Pearson's linear regression analysis. ResultsSub-group analysis showed VLDL and triglyceride levels as significant risk factors for CAD, especially in women patients. Older men (>40 years) and younger women (<40 years) reported with the highest negative correlation of IL-1 with lipid parameters, while older women showed strong positive correlation. Both younger and older men (<40 years) showed the strongest negative correlation of IL-6 with lipid parameters. Younger women showed the strongest negative correlation, while older women had the strongest positive correlation of IL-6 with lipid parameters. ConclusionOverall, this study indicates the importance of sub-group analysis in identifying comprehensive association of different parameters with the risk of CAD.