Pro-and Anti-inflammatory Cytokines Research Articles

Alpha-Pinene Decreases the Elevated Levels of Astrogliosis, Pyroptosis, and Autophagy Markers in the Hippocampus Triggered by Kainate in a Rat Model of Temporal Lobe Epilepsy.

The development and progression of temporal lobe epilepsy (TLE) are heavily influenced by inflammation, excessive activation of glial cells, and neuronal cell death. This study aimed to investigate the effects of treatment with alpha-pinene (APN) on pro-and anti-inflammatory cytokine levels, astrogliosis, pyroptosis, and autophagy markers in the hippocampus in a rat model of TLE induced by kainic acid (KA). Male Wistar rats were employed, and TLE was induced by intracerebroventricular injection of KA. APN (50mg/kg) was intraperitoneally administered for 19days, including two weeks before and five days after the administration of KA. After full recovery from anesthesia and KA injection, the seizure-related behavioral expressions were evaluated. On day 19, the hippocampal levels of IL-1β, TNF-α, progranulin, IL-10, ERK1/2, phospho-ERK1/2, NF-κB, GFAP, S100-B, NLRP1, NLRP3, caspase-1, and becline-1 were examined. The results revealed that treatment with APN significantly diminished the heightened levels of IL-1β, TNF-α, progranulin, ERK1/2, and NF-κB and reversed the reduced levels of the anti-inflammatory cytokine, IL-10, in the hippocampus caused by KA. Furthermore, administration of APN significantly reduced the levels of astrogliosis, pyroptosis, and autophagy markers in the hippocampus that were elevated by KA. It can be concluded that treatment with APN for 19days alleviated neuroinflammation by inhibiting ERK1/2 and NF-κB signaling pathways and prevented increases in astrogliosis, pyroptosis, and autophagy markers in the hippocampus in a rat model of TLE.

Variability of changes in proand antiinflammatory cytokines due to IFNα and IFNγ deficiency in patients with post-covid syndrome associated with activation of chronic herpes viral infections

Post-COVID syndrome (PCS) is characterized by long-term complications and conditions accompanied by neuroimmunoinflammation, and includes chronic fatigue syndrome (CFS) and cognitive disorders (CD), which are often associated with activation of chronic herpesvirus infections (HVI). Timely detection of symptoms and immunodiagnosis of PCS are a priority and are of undoubted interest. Objective: to clarify the levels of serum proand anti-inflammatory cytokines, alpha and gamma interferons in patients with post-COVID syndrome associated with confirmed activation of chronic herpesvirus infections. Patients (n = 60) aged from 18 to 65 years with complaints of manifestations of PCS associated with HVI were studied — the study group (SG). A survey was conducted using a modified scale-questionnaire to assess the severity of PCS symptoms in points from 0 to 4, real-time PCR of HVI (EBV, HSV1/2, VCH6, VCH8, CMV) in saliva and scrapings from the tonsils, determination of the level of IFNα and IFNγ, pro- (TNFα, IL-18, IL-1β, IL-6, IL-17A, IL-8) and anti-inflammatory (IL-4 and IL-10) cytokines in blood serum. Comparison group (CG) — 60 apparently healthy individuals. SG patients with mixed HVI with EBV dominance noted the most pronounced and persistent clinical manifestations of PCS, among which the leading place was occupied by longterm sensations of CFS and CD. A persistent multisystem inflammatory response was identified, confirmed by elevated levels of IL-6 and IL-17A, which caused severe PCS. In post-COVID period, hyperproduction of IL-1β was detected, which was accompanied by clinical manifestations of persistent neuroimmunoinflammation. At the same time, the identified deficiency of IFNα, IFNγ and dysregulatory disorders in the antiviral defense of the immune system in patients with PCS contributed to the activation of HVI. Data on the imbalance of proand anti-inflammatory cytokines in the SG were obtained, which confirms the presence of a persistent multisystem inflammatory reaction with dominance of persistent neuroimmunoinflammation, which causes severe PCS. An imbalance of the cytokine system with IFNα and IFNγ deficiency, associated with the activation of chronic HVI with EBV dominance in the post-COVID period, contributes to the development of neuroimmunoinflammation, which is accompanied by the leading clinical signs of PCS: CFS and CD.

Exosomes derived from olive flounders infected with Streptococcus parauberis: Proteomic analysis, immunomodulation, and disease resistance capacity

Multidrug-resistant Streptococcus parauberis causes high fish mortality in aquaculture, necessitating an urgent need for innovative control strategies. This study aimed to develop an immunizing agent against S. parauberis using exosomes isolated from the plasma of olive flounders infected experimentally with S. parauberis (Sp-Exo). Initially, we tested the in vitro immunomodulatory effect of Sp-Exo in murine macrophage RAW264.7 cells and compared it to that of exosomes isolated from naïve fish (PBS-Exo-treated). Notably, Sp-Exo treatment significantly (p < 0.05) upregulated pro-and anti-inflammatory cytokines (Il1β, Tnfα, and Il10), antimicrobial peptide, defensin isoforms (Def-rs2 and Def-ps1), and antiviral (Ifnβ1 and Isg15) genes. In vivo studies in larval and adult zebrafish revealed similar patterns of immunomodulation. Furthermore, larval and adult zebrafish exhibited significantly (p < 0.05) enhanced resistance to S. parauberis infection following treatment with Sp-Exo compared to that with PBS-Exo. Proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) approach revealed the presence of 77 upregulated and 94 downregulated differentially expressed proteins (DEPs) in Sp-Exo, with 22 and 37 significantly (p < 0.05) upregulated and downregulated DEPs, respectively. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Search Tool for the Retrieval of Interacting Genes/Proteins analyses revealed that these genes are associated with key pathways, such as innate immune responses, complement system, acute phase responses, phospholipid efflux, and chylomicron remodeling. In conclusion, Sp-Exo demonstrated superior immunomodulatory activity and significant resistance against S. parauberis infection relative to that on treatment with PBS-Exo. Proteomic analysis further verified that most DEPs in Sp-Exo were associated with immune induction or modulation. These findings highlight the potential of Sp-Exo as a promising vaccine candidate against S. parauberis and other bacterial infections in olive flounder.

Vitamin D3 Supplementation and Aquatic Exercise Combination as a Safe- Efficient Therapeutic Strategy to Ameliorate Interleukin-6 and 10, and Social Interaction in Children with Autism.

Increasing evidence demonstrated that there are altered levels of both pro-and anti-inflammatory cytokines in autism spectrum disorder (ASD) and pointed out that immune dysfunction may also relate to social deficits. This study aimed to investigate the effect of aquatic exercise combined with vitamin D supplementation on social interaction and two related cytokines (Interleukin-6 and Interleukin-10) in children with ASD. Forty boys with ASD (mean age: 10.90; age range: 6-14 years) were randomly assigned to the three interventions (groups 1, 2, and 3) and one control group (each 10 participants). Participants in the group 1 and 3 received a 10-week aquatic exercise program. Subjects in groups 2 and 3 took orally 50,000 IU of vitamin D3/week. This study evaluated the serum levels of IL-6 and IL-10, as well as the participants' social interaction at baseline and post-intervention. Compared to the control group, all three interventions improved social skills scores (p< 0.001). Surprisingly, the combination strategy could significantly reduce IL-6 and increase IL-10 serum levels in children with ASD. Aqua-based exercise programs combined with vitamin D supplementation are recommended to benefit children with ASD and improve social and communication dysfunction.

Pro-and Anti-Inflammatory Cytokines in Persistent Low-Level Viremia HIV-1 Patients on Combination Antiretroviral Therapy in Western Kenya

Pro-and Anti-Inflammatory Cytokines in Persistent Low-Level Viremia HIV-1 Patients on Combination Antiretroviral Therapy in Western Kenya

Anti-Arthritis Effect of Ethanol Extract of Sacha Inchi (Plukenetia volubilis L.) Leaves Against Complete Freund's Adjuvant-Induced Arthritis Model in Mice.

Sacha inchi (Plukenetia volubilis L.) is a well-known oleaginous plant used as food source and traditional medicine by indigenous people for a long time. This study was conducted to evaluate anti-arthritis effect of ethanol extract of Sacha inchi leaves and provide scientific evidence to develop the new anti-arthritis remedy from Sacha inchi. Rheumatoid arthritis model was established by injection of complete Freund's adjuvant into right hind footpads of mice and three doses of ethanol extract of Sacha inchi leaves (100, 200 and 300 mg/kg body weight) were used for treatment. The severity of arthritis was evaluated by measuring the ankle diameter and arthritic score, hematological and biochemical parameters (erythrocytes, leukocytes, lymphocytes, monocytes, granulocytes counts, erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor). The pro-and anti-inflammatory cytokines (TNF-α, INF-γ, IL-1β, IL-6, and IL-10) and the histology change of joint were also examined. All three doses of extracts significantly alleviated ankle diameter and arthritic score. Furthermore, the extracts could ameliorate the alternation of inflammatory cytokines as well histological features of CFA-induced mice. The efficacy of extract dose of 300 mg/kg body weight is comparable with reference drug (Mobic, 0.2 mg/kg body weight). This study indicates Sacha inchi leaf extract as the promising remedy for treatment of arthritis.

The fluctuations of expression profiles of critical genes in the miRNA maturation process and pro-and anti-inflammatory cytokines in the pathogenesis and progression of multiple sclerosis.

Multiple sclerosis (MS) is a central nervous system disease known for immune-mediated demyelination, inflammatory, and neurodegeneration symptoms. Discovering molecular biomarkers to classify RRMS and SPMS patients, monitor the disease activity, and response to particular treatments is one area that has received notable attraction. MicroRNA (miRNA), a single-stranded non-coding RNA molecule, is a significant regulator of gene expression recruited in pathogenic mechanisms in diverse diseases, especially cancer and MS. Also, the relapsing-remitting features of MS exhibit that both inflammatory and anti-inflammatory cytokines are effective in the progression of the disease over time. It was assessed the expression patterns of the genes (Drosha, Pasha(DGCR8), and Dicer) encoding the critical enzymes in the processing steps of miRNA maturation and major pro-inflammatory and anti-inflammatory cytokines (IFN-α, IFN-β, and IL-6) in blood cells of 40 MS patients (two groups of 10 men and women in both clinical courses of RR and SPMS patients) in comparison with 20 healthy control group (10 males and 10 females). The highest transcription activity of Drosha was observed for RRMS patients (4.2 and 3.6-fold, respectively), and the expression ratio was down regulated in male and female patients with SPMS (3.9- and 3.1-fold, respectively). Considering the studied cytokines, the increase in expression ratio of IL-6 in SPMS patients and the decrease in transcript abundance of INF-α, and INF-β cytokines are consistent with the progression of the disease. Our findings showed that the high and low transcriptional levels of the considered genes seem to be effective in the pathogenesis and progression of MS.

Determinants of serum cytokines in a population sample of healthy subjects from Iran

IntroductionCytokines are synthesized and released by immune system cells and mediate critical immune responses. Aging is associated with increased serum levels of some pro-inflammatory cytokines . A positive correlation between the concentration of several cytokines and blood pressure has been reported; higher cytokine concentrations may be related to the underlying causes of hypertension through the effects of inflammatory responses or as an independent etiology for hypertension .To assess the relationship between the serum levels of inflammatory cytokines and growth factors, with biochemical and anthropometric characteristics in healthy Iranian subjects.Material and methodsAnthropometric measurements and blood sampling were performed in 103 healthy Iranian participants. Fasting blood glucose (FBG), hs-CRP and lipid profile were measured in these participants. 12 serum cytokines/growth factors (MCP-1, TNF-α, EGF, IFN-γ, VEGF, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8 and IL-10 were measured.ResultsFBG was positively associated with serum IL-2, IL-4 and IL-1α (P = 0.044, &lt; 0.001 and = 0.017, respectively). Serum EGF and IL-4 were positively associated with age (P &lt; 0.001). IL-8 was inversely associated with SBP (P = 0.002) and gender (P = 0.028). There was a positive association between VEGF and HDL (P = 0.007). The serum levels of IFN-γ and TNF-α were positively associated with serum TG (P = 0.018 and 0.006, respectively).ConclusionsThere are associations between various pro-and anti-inflammatory cytokines in serum and several anthropometric measurements.

Outpatient management of sarcoidosis in the COVID-19 pandemic

Introduction. COVID-19 infection alters the body’s immune tolerance, which can affect the course of systemic diseases caused by alterations in immune function. Patients with sarcoidosis, just like patients with systemic diseases, have impaired immune system function. They receive immunosuppressive therapy, so they are at risk of infectious diseases, including the viral ones.Aim. To investigate the course of sarcoidosis in the period 2020-2022, the incidence of COVID-19 infection in patients treated by the pulmonologist of the sarcoidosis-polyclinic office of the Krasnoyarsk Regional Clinical Hospital and to evaluate the incidence of sarcoidosis after COVID-19.Materials and methods. 301 outpatient charts of patients diagnosed with sarcoidosis were analyzed. Anamnestic data, information on vaccination against COVID-19, results of physical examination, multispiral computed tomography of thoracic organs in dynamics, data and methods of morphological verification, the volume of the received therapy for sarcoidosis were assessed.Results. There was evidence that the combination of active sarcoidosis and COVID-19 did not contribute to a severe course of viral infection and progression in the course of granulomatosis. In patients with baseline moderate or severe pulmonary function impairment due to sarcoidosis and long-term use of systemic glucocorticosteroids, no increase in the incidence of adverse COVID-19 outcomes was noted. When analyzing fatal cases, it became known that in the first case, chronic recurrent sarcoidosis and prolonged use of systemic glucocorticosteroids were the factors determining the adverse prognosis in COVID- 19 In the second case, the combination of sarcoidosis with cardiovascular disease, diabetes mellitus, and obesity were adverse outcome factors. New cases of sarcoidosis after COVID-19 have been reported, this may be explained by the interaction between SARS-CoV-2 and human immune system, imbalance of proand anti-inflammatory cytokines, disruption of interferon production. However, this statement requires further research.

Pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases: systematic review and meta-analysis

BackgroundPro- and anti-inflammatory cytokines are acknowledged, during inflammatory bone destruction, as key regulators of osteoclast and osteoblast differentiation and activity. However, evidence regarding the exact role of pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases is unclear. We aimed to execute a systematic review and meta-analysis about the pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors levels in peri-implant diseases.MethodsThe focused question was elaborated to summarize the levels of pro-and anti-inflammatory cytokines and osteoclastogenesis-related factors in tissue samples (mRNA) and biofluids (protein levels) of patients with/without peri-implant diseases. Electronic searches of the PubMed, Cochrane Controlled Trials Registry, Web of Science, EMBASE, Scopus and Google scholar databases were conducted for publications up to March 2023. Meta-analysis evaluating the mediator´s levels (protein levels by ELISA) in peri-implant crevicular fluid (PICF) were made. The effect size was estimated and reported as the mean difference. The 95% confidence interval was estimated for each mediator, and the pooled effect was determined significant if two-sided p-values < 0.05 were obtained.ResultsTwenty-two publications were included in the systematic review (qualitative analysis), with nine of these subjected to meta-analyses (quantitative analysis). In the qualitative analysis, higher pro-inflammatory cytokines [Interleukin (IL)-1β, IL-6] and pro-osteoclastogenic mediator [Receptor Activator of Nuclear Factor-Kappa B ligand (RANKL)] levels were observed in PICF of individuals with peri-implant diseases in comparison to healthy individuals. Higher RANKL/osteoprotegerin (OPG) ratios were observed in PICF from individuals with peri-implant diseases in comparison to healthy individuals. Meta-analysis showed higher RANKL levels in diseased groups compared to controls.ConclusionsThe results showed that the levels of IL-1β, IL-6, IL-10, and RANKL/OPG are not balanced in peri-implant disease, suggesting that these mediators are involved in the host osteo-immunoinflammatory response related to peri-implantitis.

Immunological impact of cytokines on the chikungunya virus pathophysiology: A literature narrative review.

The chikungunya virus (CHIKV) is a member of the genus Alphavirus, family Togaviridae. CHIKV causes an acute systemic febrile condition, accompanied by severe polyarthralgia, intense muscle pain, and maculopapular exanthema, which may still occur in many patients. In rare cases, unusual symptoms may occur, eventually worsening the condition and resulting in a fatal outcome. It is a single-stranded, non-segmented RNA virus with a genome of approximately 11,805 nucleotides that organises a genetic and molecular chain that encodes non-structural proteins (nsP1, nsP2, nsP3, nsP4) and structural proteins (E3, E2, 6K, and E1). The fundamental role of immune response in the evolution of the disease is known. Understanding the role of immune response in the pathogenesis of CHIKV infection is challenging. In this context, innate and adaptive immune responses establish a connective interface that induces the production of various mediators that modulate the strategy of inhibiting viral replication. However, the immune escape articulated by the virus indicates that the action of pro-and anti-inflammatory cytokines contributes to the worsening of the disease and potentiates tissue damage with joint involvement. In this review, we discuss the role of the primary pro-and anti-inflammatory cytokines in the immunopathological processes of chikungunya fever.

Low vitamin D status is associated with inflammatory response in older patients with cerebral small vessel disease.

This study aimed to determine the association of the NF-κB inflammatory signaling pathway with vitamin D status in older cerebral small vessel disease (SVD) patients. We measured serum 25(OH)D, pro-and anti-inflammatory cytokines, and mRNA levels of the vitamin D-activating enzyme, CYP27B1, as well as NF-kB, COX-2, the chemokine-CCL2, IL-1β, IL-6, TNF-α, TGF-β, and IL-10, in cerebral SVD patients aged ≥60years presenting with vascular dementia and age and gender-matched healthy controls. Low vitamin D status (insufficiency: serum 25(OH)D 12-20ng/ml; deficiency: ≤12ng/ml) was more prevalent among patients compared to controls. The mRNA levels of NF-kB, COX-2, CCL2, IL-1β, and IL-6, and serum levels of pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, and TNF-α) were significantly higher in cases compared to controls. There was a significant correlation between CYP27B1 and NF-kB, COX-2, CCL2, and IL-1β gene expression. Serum IL-1α, IL-1β, and IL-6 concentrations and the expression of CCL-2, NF-kB2, and NF-kB3 genes were higher in vitamin D-deficient subjects compared to vitamin D-sufficient subjects. There was a significant negative correlation between serum 25(OH)D and IL-1α, IL-6, and TNF-α, and a positive correlation between 25(OH)D and IL-10. Low vitamin D is associated with an inflammatory response via NF-kB signaling, which could play a role in the etio-pathogenesis of SVD. Further large-scale studies are required to validate our findings.

Free and bound phenols from Cymbopogon citratus mitigated hepatocellular injury in streptozotocin-induced type 1 diabetic male rats via decrease in oxidative stress, inflammation, and other risk markers

Background/AimDiabetes mellitus is a debilitating disease still prevailing in the developing world. This study aimed to examine the protective potentials of Cymbopogon citratus extracts (crude (CCC), free (CFP), and bound phenol (CBP) fractions), in streptozotocin (STZ)-induced type 1 diabetic male rats. MethodsForty-five (45) animals of about 3–4 months were used for the study. About forty animals were induced with STZ. After induction and confirmation of diabetes, animals were grouped (five animals per group) into nine groups; group 1 (Control), group 2 received 50 mg/kg body weight (bw) (STZ). Groups 3, 4 and 5 were healthy animals and received C. citratus extracts (200 mg/kg bw CCC, 100 mg/kg bw CFP, and 100 mg/kg bw CBP) respectively; while groups 6 – 9 were diabetic group (induced with STZ) and later treated with C. citratus extracts (200 mg/kg bw CCC, 100 mg/kg bw CFP, 100 mg/kg bw CBP, and metformin (200 mg/kg bw) respectively for 14 days. Then, the animals were euthanized, blood/serum was collected, liver samples were collected and divided into two; for biochemical and histopathological studies. Liver biomarkers (ALT, AST, ALP, GGT), fructose-1,6-bisphosphatase, hexokinase, antioxidant enzymes (SOD, CAT, and GST) activities, albumin, bilirubin, hepatic glucose, GSH, MDA, pro-and anti-inflammatory cytokines concentrations, were estimated using standard protocols. ResultsOur results revealed that C. citratus extracts counteracted the deleterious effects of type 1 diabetes induction with STZ by optimizing the liver biomarkers, antioxidants enzymes, MDA and GSH levels, reducing the levels of pro-inflammatory cytokines and increasing anti-inflammatory. ConclusionOur results correlated with previous researches; the free phenols fraction revealed brilliant results above others. These suggested that C. citratus could serve as an alternative therapy in ameliorating liver complications linked to oxidative damage and inflammation in STZ-induced type-1 diabetes.

Latent tuberculosis is associated with heightened levels of pro-and anti-inflammatory cytokines among Kenyan men and women living with HIV on long-term antiretroviral therapy.

Persons with HIV (PWH) on antiretroviral therapy (ART) have persistent immune activation associated with increased risk for non-AIDS related diseases. Latent tuberculosis infection (LTBI), endemic in Africa, may contribute to this immune dysregulation. We evaluated the impact of HIV and TB co-infection on plasma pro- and anti-inflammatory cytokines among Kenyan adults. We compared data from 221 PWH on long-term ART and 177 HIV-negative adults examining biomarkers of pro-[sCD14, interleukin (IL)-2, IL-6, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-12p70, IL-17A] and anti(IL-4, IL-5, IL-13) inflammatory cytokines, by HIV/LTBI status (HIV+LTBI+, HIV+LTBI-, HIV-LTBI+, HIV-LTBI-). LTBI was diagnosed based on a positive QuantiFERON TB Gold-Plus test in the absence of active TB symptoms. Linear regression was used to evaluate the associations of HIV, LTBI, and HIV/LTBI status with biomarkers adjusting for clinical factors including HIV-specific factors. Half of the participants were women and 52% had LTBI. HIV was independently associated with higher sCD14, IL-15, IL-6, IL-4, IL-5. LTBI was independently associated with higher TNF-α, IL-12p70, IL-17A, IL-4, IL-13 in adjusted models ( P < 0.05). LTBI status was associated with higher IL-4 and IL-12p70 only among PWH, but not HIV-negative participants ( P < 0.05 for interactions). In multivariate analysis, only HIV+LTBI+ demonstrated elevated levels of TNF-α, IL-6, IL-12p70, IL-15, IL-17A, IL4, IL-5, IL-13 in comparison to the HIV-LTBI- ( P < 0.05 for all). The effect of LTBI on cytokines among PWH was independent of CD4 + T-cell count and ART duration. Despite viral suppression, persons with HIV and LTBI exhibit abnormal cytokine production accompanied by high concentrations of pro- and anti-inflammatory cytokines.

Characterization and Biological Activities of In Vitro Digested Olive Pomace Polyphenols Evaluated on Ex Vivo Human Immune Blood Cells

Olive pomace (OP) represents one of the main by-products of olive oil production, which still contains high quantities of health-promoting bioactive compounds. In the present study, three batches of sun-dried OP were characterized for their profile in phenolic compounds (by HPLC-DAD) and in vitro antioxidant properties (ABTS, FRAP and DPPH assays) before (methanolic extracts) and after (aqueous extracts) their simulated in vitro digestion and dialysis. Phenolic profiles, and, accordingly, the antioxidant activities, showed significant differences among the three OP batches, and most compounds showed good bioaccessibility after simulated digestion. Based on these preliminary screenings, the best OP aqueous extract (OP-W) was further characterized for its peptide composition and subdivided into seven fractions (OP-F). The most promising OP-F (characterized for its metabolome) and OP-W samples were then assessed for their potential anti-inflammatory properties in ex vivo human peripheral mononuclear cells (PBMCs) triggered or not with lipopolysaccharide (LPS). The levels of 16 pro-and anti-inflammatory cytokines were measured in PBMC culture media by multiplex ELISA assay, whereas the gene expressions of interleukin-6 (IL-6), IL-10 and TNF-α were measured by real time RT-qPCR. Interestingly, OP-W and PO-F samples had a similar effect in reducing the expressions of IL-6 and TNF-α, but only OP-W was able to reduce the release of these inflammatory mediators, suggesting that the anti-inflammatory activity of OP-W is different from that of OP-F.

Effects of artemisinin and hydroxychloroquine on cytokines in experimental sepsis.

Pro-and anti-inflammatory cytokines mediate the inflammatory response in sepsis. Therefore, regulation of cytokines with medications in risky situations may protect the patients from sepsis. Hydroxychloroquine and artemisinin are antimalarial drugs with immunomodulatory properties. In this study, we intended to investigate the effects of artemisinin and hydroxychloroquine on the cytokines released during sepsis in the rat model. Twenty-four rats were randomized into four groups. The control group received oral saline, the sepsis group received oral saline and intraperitoneal lipopolysaccharide toxin (LPS), the artemisinin-treated sepsis group received oral 33.33 mg/kg of artemisinin, and the hydroxychloroquinetreated sepsis group received oral 33.33 mg/kg of hydroxychloroquine before LPS injection. Three hours later, serum cytokines were measured. An increase was detected in TNF-a, IL-1, and IL-6 levels in the sepsis group compared to the control (p<0.01). Oral pretreatment with artemisinin resulted in significant downregulation only of IL-1 levels (p<0.01). Cytokines IL-1 and IL-6 were significantly downregulated in the serum of LPS-induced rats pretreated with oral hydroxychloroquine than rats with sepsis (p<0.01). Decreases observed in TNF-a and IL-10 levels were insignificant. These results demonstrated that both artemisinin and hydroxychloroquine attenuate the release of pro-inflammatory cytokines three hours after LPS-induced sepsis in rats. A significant decrease was observed in serum IL-1 and IL-6 levels with hydroxychloroquine and IL-1 levels with artemisinin. Based on our findings, we suggest that the therapeutic potential of artemisinin and hydroxychloroquine may be beneficial in preventing cytokine storm during sepsis, and further research is needed to determine the optimal timing of administration.

Biophysical and biochemical changes in skin health of healthcare professionals using respirators during COVID-19 pandemic.

Personal protective equipment, including respirator devices, has been used to protect healthcare workers (HCWs) during the COVID-19 pandemic. These are fitted to skin sites on the face to prevent airborne transmission but have resulted in reports of discomfort and adverse skin reactions from their continued usage. The present study addresses the objective changes in both the structural integrity and biological response of the skin following prolonged and consecutive use of respirators. A longitudinal cohort study, involving 17 HCWs who wear respirators daily, was designed. Changes in the barrier properties and biological response of the skin were assessed at three facial anatomical sites, namely, the nasal bridge, left cheek and at a location outside the perimeter of respirator. Assessments were made on three different sessions corresponding to the first, second and third consecutive days of mask usage. Skin parameters included transepidermal water loss (TEWL), stratum corneum (SC) hydration and erythema, as well as cytokine biomarkers sampled from sebum using a commercial tape. The cheek and the site outside the perimeter covered by the respirator presented minimal changes in skin parameters. By contrast, significant increases in both the TEWL (up to 4.8 fold) and SC hydration (up to 2.7 fold) were detected at the nasal bridge on the second consecutive day of respirator-wearing. There was a high degree of variation in the individual expression of pro-and anti-inflammatory cytokines. Increasing trends in nasal bridge TEWL values were associated with the body mass index (p<0.05). The most sensitive objective parameter in detecting changes in the skin barrier proved to be the increase in TEWL at the nasal bridge, particularly on the second day of consecutive respirator usage. By contrast, other measures of skin were less able to detect remarkable variations in the barrier integrity. Consideration for protecting skin health is required for frontline workers, who continue to wear respirators for prolonged periods over consecutive days during the pandemic.

S572 A Pilot Study for Precision Nutrition in Irritable Bowel Syndrome: In-Vitro Stimulation of Pro-and Anti-inflammatory Cytokine Release

Introduction: Inflammation plays a role in the pathogenesis of irritable bowel syndrome (IBS). Foods can trigger and exacerbate IBS flare-ups and symptoms. Diet-induced inflammation is characterized by the release of cytokines as a common feature. The lack of evidence regarding which diet is ideal for IBS underlined the need for personalized and more precise dietary treatment options. The objective of this study was to determine in-vitro the degree of blood inflammatory cytokines release in response to food antigens exposure in subjects with IBS. Methods: Blood samples were collected at Oxford Biomedical Technologies, Inc. from 12 subjects diagnosed with IBS. Whole blood was diluted with buffered physiologic saline, and then an aliquot was pipetted into eight reaction wells, each containing a single food extract. Following a predetermined incubation period at 37°C, all specimens were stored at -20°C until cytokine analysis were performed. Cytokines [interleukin-8 (IL) and IL-10)] reactivity to food antigens challenge was evaluated using Bio-Plex 200 System (Bio-Rad, CA). The IBS-Severity Scoring System (IBS-SSS) was used to measure the severity and intensity of symptoms. The questionnaire scores range from 0 to 500, with cutoffs rated as mild (75-175), moderate (175-300), and severe ( >300). The study received approval from an independent Institutional Review Board (IRB), and all statistical analyses were performed using SPSS version 27.0 (IBM Corp., NY). Results: Mean age was 52.2±17.5 years, 10 (83%) were female and had a BMI of 26.2±5.7 kg/m2. According to IBS-SSS scores, 8 (67%) of the subjects had moderate symptoms, whereas 4 (33%) had severe symptoms. We found statistically significant differences in IL-8 and IL-10 concentrations (pg/mL) release pre- vs. post-antigen exposure to broccoli [(2.17±0.75, P=0.016)]; corn [(1.25±0.44, P=0.018) and (-0.21±0.09, P=0.041)]; milk [(1.40±0.48, P=0.017); egg [(1.17±0.48, P=0.034)]; navy bean [(0.83±0.30, P=0.019) and (-0.14±0.01, P=.004)]; orange [(2.19±1.04, P=0.063)]; tomato [(2.77±1.15, P=0.038) and (-0.26±0.13; P=0.073)]; and wheat [(0.90±0.36, P=0.033) and (-0.27±0.08, P=0.011)] respectively. Conclusion: The findings from this study generate much-needed data to aid the understanding of non-physiological inflammatory responses to foods which can optimize targeted dietary therapy for IBS. Further work is needed to develop a diagnostic assay that could be used to create a precise and personalized diet for clinical practice.

Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA.

Malaria is the most lethal parasitic disease worldwide; men exhibit higher mortality and more severe symptomatology than women; however, in most studies of immune response in malaria, sex is not considered a variable. Sex hormones 17β-oestradiol and testosterone are responsible for the main physiological differences between sexes. When interacting with their receptors on different immune cells, they modify the expression of genes that modulate cell proliferation, differentiation, and synthesis of cytokines. The immunosuppressive activity of testosterone is well accepted; however, its participation in the sexual dimorphism of the immune response to malaria has not been studied. In this work, we analysed whether altering the concentration of testosterone, through increasing the concentration of this hormone for exogenous administration for three weeks, or gonadectomy before infection with Plasmodium berghei ANKA affects different cells of the immune response necessary for parasite clearance. We also assessed the concentration of pro-and anti-inflammatory cytokines in male and female CBA/Ca mice infected or not with the parasite. Our results show that testosterone changes affect females more than males, resulting in sex-associated patterns. Testosterone administration increased parasitaemia in intact males while reducing it in intact females leading to a dimorphic pattern. In addition, gonadectomy increased parasitaemia in both sexes. Moreover, testosterone administration prevented both weight loss caused by the infection in females and hypothermia in gonadectomized mice of both sexes. Boosting testosterone concentration increased CD3+ and CD8+ populations but decreased the B220+ cells exclusively in females. Additionally, testosterone reduced IFN-γ concentration and increased IL-6 levels only in females, while in males, testosterone increased the number of NK cells. Finally, gonadectomy decreased TNF-α concentration in both sexes. Our results demonstrate that testosterone induces different patterns depending on sex and testosterone concentration. The results of this work contribute to understanding the impact of modifying testosterone concentration on the immune response specific against Plasmodium and the participation of this hormone in sexual dimorphism in malaria.

Different inoculum of Leishmania braziliensis concentrations influence immunopathogenesis and clinical evolution in the ear dermis hamster model of cutaneous leishmaniasis.

The golden hamster (Mesocricetus auratus) is commonly used as a promising model for Leishmania braziliensis infection developing skin-ulcerated lesions. However, different protocols using high concentration of parasites inoculated in the footpad result in severe clinical disease. Here, we further investigate the outcome of the site of infection and concentration of L. braziliensis parasites inoculated on the immunopathogenesis and clinical evolution. Initially, hamsters were infected in the ear dermis or hind footpad with a concentration of 1 × 105 parasites. Animals infected in the ear dermis developed a disease, with an increased parasite load that more closely resembled human cutaneous leishmaniasis lesions comparing to the group infected in the footpad. Next, we evaluated if different parasite concentrations (104 , 105 and 106 ) inoculated in the ear dermis would impact the course and clinical aspects of infection. Hamsters infected with 104 and 105 parasites developed mild lesions compared to the group infected with 106 that presented severe and persistent lesions. The parasite load varied between the different parasite concentrations. The inflammatory response was more intense when infection was initiated with 106 parasites accompanied by an increased initial expression of IL-4, IL-10 and arginase in the lymph node followed by expression of both pro-and anti-inflammatory cytokines comparing to groups infected with 104 and 105 parasites. In conclusion, the number of parasites inoculated, and the initial site of infection could influence the inflammatory response, and clinical presentation. Our results suggest that the ear dermis infection model induces a chronic disease that relates to immunopathological aspects of CL natural infection.