Immunopharmacology and Immunotoxicology最新文献

{"title":"Artificial liver support systems bridge severe immune-mediated hepatotoxicity to clinical recovery.","authors":"Qiangfeng Wang, Cheng Xiao, Peipei Hu, Xiuming Zhang, Jiangshan Lian, Xingyun Su, Xiongfei Yu, Jiajia Chen, Yulong Zheng","doi":"10.1080/08923973.2025.2454030","DOIUrl":"10.1080/08923973.2025.2454030","url":null,"abstract":"<p><strong>Background: </strong>The incidence of hepatic immune-related adverse events has increased with the wide use of immune checkpoint inhibitors (ICIs), some immune-mediated hepatotoxicity (IMH) cases are severe and lack of clinical recommendations.</p><p><strong>Objective: </strong>This study aimed to evaluate the efficacy of artificial liver support systems (ALSSs) in the treatment of IMH.</p><p><strong>Methods: </strong>This retrospective case series included six patients with grade 4 hepatotoxicity with high bilirubin induced by ICIs treated between 1 January 2019 and 31 December 2021. All patients received ALSS treatment.</p><p><strong>Results: </strong>After treatment and recovery, four of the six patients experienced improvement in hepatotoxicity, with total bilirubin (TBIL) levels reduced to ≤ grade 2, and two patients achieved complete recovery (TBIL grade = 0).</p><p><strong>Conclusion: </strong>ALSS serve as a therapeutic option for severe IMH.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"194-200"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vildagliptin attenuates doxorubicin-induced hepatotoxicity via activating Nrf2/HO-1 and SIRT1 and suppressing NF-κB signals in rats.","authors":"Heba M Mahmoud, Emad H M Hassanein, Marwa M Khalaf","doi":"10.1080/08923973.2025.2482863","DOIUrl":"https://doi.org/10.1080/08923973.2025.2482863","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is an anticancer commonly employed in cancer treatment. However, the clinical application of DOX is associated with hepatotoxicity. Vildagliptin is an anti-hyperglycemic agent that inhibits the dipeptidyl peptidase-4 enzyme. Besides being used in managing type-2 diabetes, vildagliptin showed potential anti-inflammatory, antioxidant, and other activities.</p><p><strong>Objective: </strong>Our investigation targeted the hepatoprotective effects of vildagliptin against DOX-induced hepatotoxicity.</p><p><strong>Methods: </strong>Vildagliptin was given in a dose of 30 mg/kg, once daily; p.o. for 2 weeks while DOX was injected in a single dose of 30 mg/kg, i.p.</p><p><strong>Results: </strong>Vildagliptin effectively decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, while it effectively elevated serum total protein (TP) level. Histologically, vildagliptin administration resulted in significant hepatoprotective efficacy with abundant figures of normal hepatocytes. Moreover, vildagliptin considerably decreased lipid peroxidation biomarker malondialdehyde (MDA), and the cytokines interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and cyclooxygenase (COX)-2, while it remarkably boosted the antioxidative defenses of glutathione (GSH) and catalase (CAT). Dual antioxidant and anti-inflammatory activities were mediated by upregulating nuclear factor (erythroid-derived 2)-like 2 (Nrf2), silent information regulator 1 (SIRT1), and heme oxygenase (HO-1) and suppressing the nuclear factor kappa B (NF-κB) signals. Finally, vildagliptin alleviated apoptosis by downregulating hepatic p53 and cytochrome (Cyt)-C.</p><p><strong>Conclusion: </strong>Our findings suggest that vildagliptin improved hepatocellular architecture and reduced hepatic oxidative injury, inflammation, and apoptosis associated with DOX treatment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D and canagliflozin combination alleviates Parkinson's disease in rats through modulation of RAC1/NF-κB/Nrf2 interaction.","authors":"Sara Kamal Rizk, Eman A Ali, AlZahraa A M Sheref, Sara G Tayel, Sara A El Derbaly","doi":"10.1080/08923973.2025.2481849","DOIUrl":"https://doi.org/10.1080/08923973.2025.2481849","url":null,"abstract":"<p><strong>Objective: </strong>Oxidative stress and neuroinflammation are crucial factors in the pathogenesis of Parkinson's disease (PD). Vitamin D (Vit D) and canagliflozin (CAN) are known to have anti-inflammatory and antioxidant properties. Together, they target key molecular pathways involved in PD, including oxidative stress and neuroinflammation, specifically, the small GTPase protein (RAC1)/nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, which regulates brain's oxidative stress and inflammation. This study investigates the effects of Vit D and CAN alone and in combination in a rat model of PD.</p><p><strong>Materials and methods: </strong>Fifty male Wistar rats were assigned to five groups (<i>n</i> = 10), including control, rotenone (ROT), Vit D + ROT, CAN + ROT, and Vit D + CAN + ROT. We assessed weight changes, brain weight, neurobehavioral functions, biochemical markers, and immunohistopathology of brain tissues.</p><p><strong>Results: </strong>The results showed that Vit D treatment was more effective than CAN in alleviating PD symptoms, with the combination of Vit D and CAN offering the best therapeutic outcome. This combination therapy significantly improved serum Vit D, striatal dopamine (DA) levels, antioxidant status (reduced glutathione (GSH) and catalase (CAT), reduced oxidative stress (malondialdehyde (MDA)), and ameliorated inflammation (tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10)). Additionally, the combination therapy modulated the expression of RAC1, NF-κB, Nrf2, vitamin D receptors (VDR), and vitamin D-binding protein (DBP) and immunoexpression of tyrosine hydroxylase (TH), and α-synuclein (α-SYN).</p><p><strong>Conclusion: </strong>These findings suggest that Vit D and CAN synergistically modulate the RAC1/NF-κB/Nrf2 pathway, leading to improved neuroprotection in PD.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-17"},"PeriodicalIF":2.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of roflumilast on cyclophosphamide-induced ovarian toxicity in rats: role of SIRT1/Nrf2/nF-ĸB pathway.","authors":"Salma A El-Marasy, Hadir Farouk, Marwa S Khattab, Marwan Abdelbaset","doi":"10.1080/08923973.2025.2482804","DOIUrl":"https://doi.org/10.1080/08923973.2025.2482804","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the possible protective effect of roflumilast (RFL) on cyclophosphamide (CP)-induced ovarian toxicity as well as the possible underlying mechanism.</p><p><strong>Material and methods: </strong>Female Wistar rats received the vehicle (<i>n</i> = 6) or CP (200 mg/kg, i.p.). The other 2 groups (<i>n</i> = 6 for each) were orally pretreated with RFL at dosages of 0.5 and 1 mg/kg, respectively, for 14 days and then after one hour of RFL administration on the 14th day, rats were intraperitoneally administered a single dose of CP. Serum and tissue samples were collected. Biochemical, real-time polymerase chain reaction, histopathological and immunohistopathological examination were carried out.</p><p><strong>Results: </strong>RFL significantly elevated serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) compared to the CP group. RFL remarkably elevated ovarian contents of Sirtuin-1 (SIRT1), heme oxygenase-1 (HO-1), and reduced nuclear factor-kappa B (NF-ĸb) p65/NF-ĸB ratio as compared to control CP group. Compared to the CP group, RFL significantly elevated Nrf2 gene expression, reduced malondialdehyde (MDA), and elevated the reduced glutathione (GSH) ovarian content. It also reduced the protein expression of TNF-α and caspase-3.</p><p><strong>Conclusion: </strong>It can be concluded that RFL (0.5 and 1 mg/kg) protected rats against CP-induced ovarian toxicity <i>via</i> altering the SIRT1/Nrf2/NF-ĸB pathway, ameliorating histopathological changes in addition to its anti-apoptotic effect.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-10"},"PeriodicalIF":2.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-inflammatory effects of vitamin B6 on neuroinflammation and neuronal damage caused by 1,2-diacetylbenzene in BV2 microglial and sH-SY5Y cells.","authors":"Hai Duc Nguyen, Won Hee Jo, Ngoc Hong Minh Hoang, Min-Sun Kim","doi":"10.1080/08923973.2025.2469216","DOIUrl":"https://doi.org/10.1080/08923973.2025.2469216","url":null,"abstract":"<p><strong>Background: </strong>The pathophysiology of cognitive impairment has recently focused on 1,2-Diacetylbenzene (DAB), B vitamins, tau hyperphosphorylation, and neuroinflammation. While past evidence shows that vitamin B6 influences the immune system, the molecular processes behind DAB-induced neuroinflammation and cognitive impairment remain largely unknown. This study aimed to assess the protective roles of vitamin B6 against DAB-induced toxicity in BV2 microglial and SH-SY5Y cells.</p><p><strong>Methods: </strong><i>In vitro</i> approaches included Western blot, qRT-PCR, cell viability assays, immunocytochemistry, reactive oxygen species, and nitrite assays. For <i>in silico</i> analysis, we utilized Metascape, Cytoscape, MIENTURNET, and molecular docking.</p><p><strong>Results: </strong>Vitamin B6 suppressed the TLR4/NF-κB pathway and the TREM-1/DAP12/NLRP3/caspase-1/IL1B pathway in DAB-activated BV2 cells. Additionally, it reduced reactive oxygen species and nitric oxide levels while increasing Nrf2 and IL10 production. In SH-SY5Y cells, vitamin B6 inhibited GSK-3β Tyr216, tau hyperphosphorylation, and β-amyloid production. The <i>in silico</i> analysis identified 'positive regulation of NF-κB transcription factor activity,' 'regulation of IL-6 production,' and 'positive regulation of adaptive immune response' as key molecular mechanisms linked with DAB-induced cognitive impairment and targeted by vitamin B6. Core genes, miRNAs, and transcription factors included IL1β, IL6, IL10, TNF, hsa-miR-155-5p, hsa-miR-203a-3p, hsa-miR-106a-5p, hsa-miR-26a-5p, CEBPB, and PXR.</p><p><strong>Conclusion: </strong>Our findings indicate that vitamin B6 may protect against DAB-induced cognitive impairment by attenuating key inflammatory pathways, reducing oxidative stress, and inhibiting tau hyperphosphorylation, β-amyloid production, and GSK-3β Tyr216 phosphorylation. This highlights its potential as a therapeutic agent for cognitive impairment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.9,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The protective effects of a single dose myricetin application on CLP-induced rat sepsis model by analyzing some immune mechanisms.","authors":"Ismail Can, Ali Guraslan, Omer Faruk Baser, Gulfem Nur Yıldız, Ihsan Toplaoglu, Selina Aksak Karamese, Murat Karamese","doi":"10.1080/08923973.2025.2469227","DOIUrl":"10.1080/08923973.2025.2469227","url":null,"abstract":"<p><strong>Introduction: </strong>In this study, our aim was to investigate the protective effects of myricetin (single dose-100 mg/kg) on CLP-induced rat sepsis model by analyzing some immune mechanisms including inflammation and oxidative stress by different techniques such as Immunohistochemistry, ELISA, tissue biochemistry and Western Blotting.</p><p><strong>Methods: </strong>Twenty-eight Wistar albino rats were divided into 4 groups. The pro-inflammatory and anti-inflammatory cytokine levels were measured by ELISA technique. CD68 and Nuclear-Factor-Kappa-B (NF-κB) positivity rates were detected by IHC. Some of oxidative stress parameters were measured by tissue biochemistry, while Toll-like receptor-4 (TLR4) expression others were detected by Western blot technique.</p><p><strong>Results: </strong>Sepsis caused a significant increase in all pro-inflammatory cytokine and oxidant levels. Also, it led to an increase in the positivity of CD68 and NF-κB markers as well as the expression levels of TNF-alpha, IL-1-beta, TLR4, Keap-1. However, single dose myricetin application normalized pro-inflammatory cytokine levels, increased anti-oxidant and anti-inflammatory cytokine levels, decreased positivity of CD68 and NF-κB and increased NRF2 and HO-1 expressions.</p><p><strong>Discussion: </strong>As a conclusion, the beneficial effect of myricetin on lung injury also involved inhibition of TLR4/NF-κB pathway, suppression of proinflammatory cytokines and induction of anti-inflammatory cytokine production, regulation of oxidant and anti-oxidant system parameters, and activating the NRF2/Keap1/HO-1 pathway.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Punicalagin ameliorates lipopolysaccharide-induced inflammatory response in dental pulp cells via inhibition of the NF-κB/Wnt5a-ROR2 pathway.","authors":"Yumeng Yang, Ke Deng, Shan Jiang, Xiaolan Guo, Yiming Zhong, Buling Wu, Liu Wei","doi":"10.1080/08923973.2025.2470343","DOIUrl":"10.1080/08923973.2025.2470343","url":null,"abstract":"<p><strong>Introduction: </strong>Punicalagin (PCG) is a major polyphenolic component with potent anti-inflammatory, anti-atherogenic, anti-cancer, and antioxidant activities. This study aimed to investigate the impact and underlying mechanisms of PCG on lipopolysaccharide (LPS)-induced dental pulpitis.</p><p><strong>Methods: </strong>A rat pulpitis model was constructed, and the infected pulp was covered with a PCG collagen sponge. <i>In vitro</i>, dental pulp cells (DPCs) were isolated, and the effects of LPS and PCG on cell viability were assessed. The expression levels of inflammation-related factors were investigated by qRT-PCR and ELISA. The Nuclear Factor kappa B (NF-κB) transcription factors and Wnt family member 5a-Receptor tyrosine kinase like Orphan Receptor 2 (Wnt5a-ROR2) levels were evaluated by immunofluorescence staining and Western blotting.</p><p><strong>Results: </strong>We demonstrated that the PCG collagen sponge effectively reduced the infiltration of inflammatory cells in the pulp. PCG significantly alleviated the inflammatory response by reducing the mRNA expression levels of IL-1β, IL-6, IL-8, ICAM-1, and VCAM-1 and the secretion of IL-6 and IL-8 in a concentration-dependent manner. Immunofluorescence staining showed that the activation of the NF-κB pathway was hindered by PCG, which affected with the nuclear translocation of P65. PCG reduced the phosphorylation levels of P65 and IκBα and suppressed the expression levels of Wnt5a and ROR2 induced by LPS. The NF-κB inhibitor Bay11-7082 reduced the activation of the NF-κB/Wnt5a-ROR2 pathway and the inflammatory response; the application of PCG significantly augmented this inhibitory effect.</p><p><strong>Discussion: </strong>PCG demonstrated an anti-inflammatory effect in LPS-induced DPCs by targeting the NF-κB/Wnt5a-ROR2 signaling pathway.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reno-protective impact of diosmin and perindopril in amikacin-induced nephrotoxicity rat model: modulation of SIRT1/p53/C-FOS, NF-κB-p65, and keap-1/Nrf2/HO-1 signaling pathways.","authors":"Nashwa Abdelaala, Ehab A M El-Shoura, Marwa M Khalaf, Dalia Zafaar, Ahmed A N Ahmed, Ahmed M Atwa, Basel A Abdel-Wahab, Yasmine H Ahmed, Ahmed Abomandour, Esraa A Salem","doi":"10.1080/08923973.2025.2469220","DOIUrl":"10.1080/08923973.2025.2469220","url":null,"abstract":"<p><strong>Purpose: </strong>Amikacin (AMC), an aminoglycoside antibiotic known for its rapid and potent bactericidal activity, is also associated with nephrotoxicity. Diosmin and perindopril have been reported to improve renal function and hold promise as therapeutic agents for preventing drug-induced nephrotoxicity. This study aimed to investigate the protective effect of Diosmin and perindopril, either alone or in combination, against renal damage induced by AMC toxicity and to elucidate the underlying mechanisms.</p><p><strong>Materials and methods: </strong>The researchers evaluated the impact of Diosmin (50 mg/kg, orally) and perindopril (2 mg/kg, intraperitoneally) on AMC-induced kidney injury (1.2 g/kg, intraperitoneally) in rats. Invasive blood pressure, serum kidney function and toxicity parameters, oxidative stress biomarkers, and inflammatory cytokine levels in serum and renal tissue were assessed. Histopathological changes in the kidney were examined using hematoxylin and eosin (H&E) staining, electron microscopy, and immunohistochemical analysis. The molecular mechanisms underlying the protective effect of the combination pretreatment on kidney injury were investigated using enzyme-linked immunosorbent assay (ELISA) and Western blotting techniques.</p><p><strong>Results: </strong>The findings demonstrated that the combination therapy improved kidney function by attenuating pathological changes observed in H&E staining including tubular necrosis and glomerular damage, in addition to reducing levels of kidney function including serum levels of creatinine compared to the AMC group, blood urea nitrogen (BUN) uric acid, and albumin. Mean arterial blood pressure, and toxicity markers including Kidney Injury Molecule-1 (KIM-1), Cystatin-c were also decreased in samples of combination group compared to AMC group. Furthermore, the protective combination therapy downregulated NF-κB-p65, P53, Keap-1, and C-FOS, while upregulating Mammalian sirtuin 1 (SIRT1), inhibitor of nuclear factor kappa B (Iκβ), nuclear factor erythroid 2-related factor 2 (Nrf2), and Heme oxygenase-1 (HO-1) levels.</p><p><strong>Conclusions: </strong>The findings reveal the potential clinical application of combining Diosmin and perindopril to reduce AMC-induced nephrotoxicity, which requires further research in clinical settings.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-18"},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crocin as a potential therapeutic agent for multiple sclerosis: insights from experimental autoimmune encephalomyelitis model in mice.","authors":"Alireza Pazoki, Mahbobeh Askaripour, Simin Zargarani, Esmaeil Yazdanpanah, Dariush Haghmorad","doi":"10.1080/08923973.2024.2445747","DOIUrl":"https://doi.org/10.1080/08923973.2024.2445747","url":null,"abstract":"<p><strong>Objective: </strong>Multiple sclerosis (MS) is a prevalent autoimmune disorder characterized by neuroinflammation and demyelination in the central nervous system (CNS), leading to neurological dysfunction. Despite advances in treatment, there remains an unmet need for safe and effective therapies. Crocin, a bioactive constituent of saffron, has demonstrated anti-inflammatory and immunoregulatory properties in various disease models. This study investigates the therapeutic potential of Crocin in a murine model of MS, experimental autoimmune encephalomyelitis (EAE).</p><p><strong>Methods and results: </strong>Female C57BL/6 mice were induced with EAE and treated with different doses of Crocin. Clinical severity, CNS pathology, T cell proliferation, cytokine production, and transcription factor expression were assessed. Crocin-treated mice showed reduced clinical severity, inflammation, and demyelination in the CNS compared to controls. Moreover, Crocin attenuated T cell proliferation and modulated cytokine production, promoting an anti-inflammatory cytokine profile while suppressing pro-inflammatory cytokines. Additionally, Crocin altered the expression of transcription factors associated with T cell differentiation, favoring regulatory T cell responses.</p><p><strong>Discussion: </strong>These findings suggest that Crocin exerts therapeutic effects in EAE by modulating neuroinflammation and immune responses. Further studies are warranted to elucidate the mechanisms underlying Crocin's immunomodulatory properties and its potential as a treatment for MS.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pesticide exposure promotes disease activity by decreasing lymphoproliferative activity and increasing IL-4 production in systemic sclerosis patients.","authors":"Ahmad Alsulimani, Shukla Das, Naseem Akhter, Abrar Ahmad, Arshad Jawed, Saba Beigh, Mazin A Zamzami, Salwa Al-Thawadi, Mohamed Yahya Alfoud, Basu Dev Banerjee, Sajad Ahmad Dar","doi":"10.1080/08923973.2024.2445731","DOIUrl":"https://doi.org/10.1080/08923973.2024.2445731","url":null,"abstract":"<p><strong>Background: </strong>One of the common findings in systemic sclerosis (SSc) patients has been long-term exposure to environmental toxins such as pesticides. However, the data available shows an equivocal association between pesticide exposure and autoimmunity in SSc.</p><p><strong>Methods: </strong>We investigated the levels of organochlorine pesticides (OCPs) in blood of 20 SSc patients and 17 healthy controls, and also studied their effect <i>in-vitro</i> on T lymphocytes and their functional responses.</p><p><strong>Results: </strong>We found higher levels of hexachlorocyclohexane (HCH- α-, β-, and γ) and o,p'-dichlorodiphenyltrichloroethane (DDT) metabolite (p,p΄-DDE) in blood of SSc patients. <i>In vitro</i> treatment of SSc patient PBMCs with either of HCH (100 mM) or DDT (50 µM) caused a significant increase merely in CD8⁺ memory (CD8⁺CD45RO⁺) T lymphocytes. We also observed reduced FoxP3 expression in CD4⁺CD25⁺ (regulatory T cells) of SSc patients. Neither HCH nor DDT exposure of SSc PBMCs altered significantly the secretion of IL-2, IL-10, or IFN-γ, but both of these pesticides elevated their IL-4 (a pro-fibrotic cytokine) secretion.</p><p><strong>Conclusion: </strong>Taken together, our findings indicate that persistent exposure to these OCPs results in decreased lymphoproliferative activity which promotes disease activity by producing pro-fibrotic cytokine(s). Thus, SSc patients are less able to initiate or augment an immune response to foreign antigens, when there is substantial suppression of lymphocyte function, which increases their susceptibility to infection. Strategies to prevent and control pesticide exposure may play an important role in reducing the morbidity and mortality associated with this disease.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}