[Consideration on implementation of co-administration of Seasonal Influenza and COVID-19 vaccines during pandemic in China].

Influenza is an infectious respiratory disease caused by the influenza viruses. Older people, infants and people with underlying medical conditions could have a higher risk of severe influenza symptoms and complications. The co-infection of Coronavirus Diseases 2019 (COVID-19) with influenza viruses could lead to the complication of prevention, diagnosis, control, treatment, and recovery of COVID-19. Influenza vaccine and COVID-19 vaccine overlapped in target populations, vaccination time, and inoculation units. Although there was insufficient evidence on the immunogenicity and safety of co-administration of influenza vaccine and COVID-19 vaccine, World Health Organization and some countries recommended co-administration of inactivated influenza vaccine and COVID-19 vaccine. This review summarized domestic and international vaccination policies and research progress, and put forward corresponding suggestions in order to provide scientific support for the formulation of vaccination strategy on seasonal influenza vaccine and COVID-19 vaccine.

Dysregulation of TFDP1 and of the cell cycle pathway in high-grade glioblastoma multiforme: a bioinformatic analysis.

Despite extensive research, the prognosis of high-grade glioblastoma multiforme (GBM) has improved only slightly because of the limited response to standard treatments. Recent advances (discoveries of molecular biomarkers) provide new opportunities for the treatment of GBM. The aim of the present study was to identify diagnostic biomarkers of high-grade GBM. First, we combined 3 microarray expression datasets to screen them for genes differentially expressed in patients with high-grade GBM relative to healthy subjects. Next, the target network was constructed via the empirical Bayesian coexpression approach, and centrality analysis and a molecular complex detection (MCODE) algorithm were performed to explore hub genes and functional modules. Finally, a validation test was conducted to verify the bioinformatic results. A total of 277 differentially expressed genes were identified according to the criteria P < 0.05 and |log2(fold change)| ≥ 1.5. These genes were most significantly enriched in the cell cycle pathway. Centrality analysis uncovered 9 hub genes; among them, TFDP1 showed the highest degree of connectivity (43) and is a known participant in the cell cycle pathway; this finding pointed to the important role of TFDP1 in the progression of high-grade GBM. Experimental validation mostly supported the bioinformatic results. According to our study results, the gene TFDP1 and the cell cycle pathway are strongly associated with high-grade GBM; this result may provide new insights into the pathogenesis of GBM.

Efficacy of telbivudine treatment for hepatitis B e antigen-positive chronic hepatitis B patients with poor response to adefovir dipivoxil.

Telbivudine (LdT) has demonstrated potent antiviral activity in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B patients (CHB), but data on its efficacy in NA-experienced patients are limited. The aim of this study was to investigate the effect of LdT in hepatitis B e antigen-positive CHB patients with poor response to initial adefovir dipivoxil (ADV). Forty-two CHB patients with HBV DNA > 4 log10  copies/mL after 12 months of ADV monotherapy were enroled in the study and thereafter treated with LdT 600 mg daily for 18 months. Telbivudine led to a rapid decrease in viral load, and viral replication was persistently suppressed with a reduction of 2.26 log10  copies/mL 18 months after LdT treatment. The rates corresponding to virological and biochemical response at the end of observation were 97.6% (41/42) and 65.8% (25/38), respectively. HBeAg loss was found in 30.8% (12/39) of patients, while HBeAg/anti-HBe seroconversion was found in 17.9% (7/39). Only one patient was detected to have LdT-associated mutation, and no severe adverse events were reported. Optimization therapy with LdT monotherapy may be a good choice for CHB patients with poor response to ADV, and switching to LdT may be the most cost-effective rescue therapeutic strategy for patients with poor response to initial ADV monotherapy.

Review of research pertaining to the effect of tumor-derived exosomes on natural killer cells.

Tumor-derived exosomes (TDEs) play critical roles in many aspects of cancer progression. There have been several advances in cancer immunotherapy in recent years. A major challenge, however, has been addressed to the role of TDEs in tumor cell immune escape through their influence on the antitumor immunity of natural killer (NK) cells, a key type of immune cell. In this review, we present our overview of the effects of different TDEs on NK cell activation and NK cell toxicity. Studies on mechanism suggest that TDEs mainly affect the immune response of NK cells by inhibiting activated receptors on the surface of NK cells and downregulating the NK recognition ligand MICA/B on the tumor cell surface. In addition, a summary was documented on how to restore the cytotoxicity of NK cells and improve the drug's ability to recognize tumor cells, and a detailed explanation was also provided on the mechanism of action of the drug.

The impact of probiotics on gut microbiota in the eradication of Helicobacter pylori infection: a systematic review.

OBJECTIVE: The effect of probiotics supplementation on the gut microbiota in Helicobacter pylori (H. pylori) eradication therapy is controversial. Therefore, this review aimed to illustrate changes in the gut microbiota after standard eradication therapy with probiotics supplements. MATERIALS AND METHODS: A computerized literature search in PubMed, Cochrane Library, Web of Science, and Embase database was performed up to February 1st, 2022, with English language restriction. The extracted outcomes were analyzed, including gut microbiota, adverse effects, and eradication rate. RESULTS: 13 studies reported data on 777 participants who were finally eligible for this systematic review. All of them are randomized controlled trials investigating the effect of H. pylori eradication with probiotics supplementation therapy on gut microbiota. Probiotics supplementation seems to play a positive role in restoring the gut microbiota during H. pylori eradication therapy. However, the changes in the gut microbiota are still controversial. The included studies had significant heterogeneity in the study population, diagnostic methods of H. pylori infection, and detection techniques of the gut microbiota and probiotics species. CONCLUSIONS: The results provided a basis for the rational selection of probiotics in the H. pylori eradication process. Probiotic supplementation might keep the balance of gut microbiota and reduce the gastrointestinal adverse effects of antibiotics, but whether it could improve the eradication rate or not is a debatable point. Therefore, more research is needed to provide evidence.

Polymorphisms in the promoter of the CD14 gene and their associations with susceptibility to pulmonary tuberculosis.

Although the role of CD14 in recognizing Mycobacterium tuberculosis is well-understood, the possible role of polymorphisms in susceptibility to develop tuberculosis remains unclear. This study evaluates whether there is an association of polymorphisms within the promoter of the CD14 gene with susceptibility to pulmonary tuberculosis. In a case-control study, we genotyped the eight known single nucleotide polymorphisms SNPs within the promoter of the CD14 gene of 698 Han Chinese subjects. Statistically significant differences between tuberculosis patients and healthy controls were found for G-1619A, T-1359G, A-1145G, and C-159T. The haplotype-GGGT, composed of these four SNPs, exhibited a significant association with the disease. Furthermore, expression levels of soluble CD14 were significantly higher in tuberculosis patients with the GGGT haplotype than with other haplotypes, while IgE expression levels were significantly reduced. Our results suggest that these four SNPs within the promoter of the CD14 gene are associated with susceptibility to pulmonary tuberculosis.

IL-10 contributes to the suppressive function of tumour-associated myeloid cells and enhances myeloid cell accumulation in tumours.

Studies have revealed that tumour-associated myeloid cells (TAMC) are one of the major sources of IL-10 in tumour-bearing mice. However, the significance of TAMC-derived IL-10 in tumour immunity is poorly understood. Here, we show that IL-10 blockade or IL-10 deficiency reduces the capacity of TAMC in suppressing the proliferation of P1A-specific CD8 T cells. In the spleen, IL-10-deficient and wild-type (WT) mice bearing large tumour burdens have similar TAMC populations. The tumours from IL-10-deficient mice, however, have reduced numbers of TAMC compared with tumours from their WT counterparts. IL-10⁻/⁻ RAG-2⁻/⁻ mice also had reduced numbers of TAMC compared with tumours from IL-10⁺/⁺ RAG-2⁻/⁻ mice; therefore, the reduction in TAMC in IL-10-deficient tumours was not because of adaptive immune response in tumours. Adoptively transferred tumour antigen-specific CD8 T cells expanded more efficiently within tumours in IL-10⁻/⁻ RAG-2⁻/⁻ mice than in tumours from IL-10⁺/⁺ RAG-2⁻/⁻ mice. Cytotoxic T lymphocyte adoptive transfer therapy prevented tumour evasion in IL-10⁻/⁻ RAG-2⁻/⁻ mice more efficiently than in IL-10⁺/⁺ RAG-2⁻/⁻ mice. Thus, IL-10 enhances the accumulation of myeloid cells in tumours, and TAMC-derived IL-10 suppresses the activation and expansion of tumour antigen-specific T cells.

Cytotoxic T lymphocytes to an unmutated tumor rejection antigen P1A: normal development but restrained effector function in vivo.

Unmutated tumor antigens are chosen as primary candidates for tumor vaccine because of their expression on multiple lineages of tumors. A critical issue is whether unmutated tumor antigens are expressed in normal cells, and if so, whether such expression imposes special restrictions on cytotoxic T lymphocyte (CTL) responses. In this study, we use a transgenic approach to study the development and effector function of T cells specific for P1A, a prototypical unmutated tumor antigen. We report here that although P1A is expressed at low levels in normal tissues, including lymphoid tissues, the P1A-specific transgenic T cells develop normally and remain highly responsive to the P1A antigen. The fact that transgenic expression of P1A antigen in the thymus induces T cell clonal deletion demonstrates that normal hematopoietic cells can process and present the P1A antigen and that P1A-specific T cells are susceptible to clonal deletion. By inference, P1A-specific T cells must have escaped clonal deletion due to low expression of P1A in the thymus. Interestingly, despite the fact that an overwhelming majority of T cells in the T cell receptor for antigen (TCR)-transgenic mice are specific for P1A, these mice are no more resistant to a P1A-expressing plasmocytoma than nontransgenic littermates. Moreover, when the same TCR-transgenic mice were challenged simultaneously with B7-1(+) and B7-1(-) tumors, only B7-1(+) tumors were rejected. Therefore, even though P1A can be a tumor rejection antigen, the effector function of P1A-specific CTL is restrained in vivo. These results have important implications for the strategy of tumor immunotherapy.

B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8(+) T lymphocytes in vivo.

B7H/B7RP (hereby called B7H) is a new member of the B7 family of costimulatory molecules and interacts with inducible costimulatory molecule (ICOS). Its function for CD8 T cells has not been reported. We report here that expression of B7H on the tumor cells reduced tumorigenicity and induced immunity to subsequent challenge with parental tumor cells. The immune protection correlates with an enhanced cytotoxic T lymphocyte (CTL) response against P1A, the major tumor antigen expressed in the J558 tumor. To understand the mechanism of immune protection, we adoptively transferred transgenic T cells specific for tumor antigen P1A into mice that bore P1A-expressing tumors. We found that while the transgenic T cells divided faster in mice bearing the B7H(+) tumors, optimal B7H-induced clonal expansion of P1CTL required costimulation by B7-1 and B7-2 on the endogenous host antigen-presenting cells (APCs). Interestingly, when B7H(+) and B7H(-) tumors were coinjected, P1CTL selectively eliminated the B7H(+) tumor cells. Moreover, B7H expressed on the tumor cells made them highly susceptible to destruction by CTL in vivo, even if the CTL was administrated into mice with large tumor burdens. Tumors that recurred in the P1CTL-treated mice lost transfected B7H and/or H-2L(d), the class I molecule that presents the P1A peptide. Taken together, our results reveal that B7H costimulates clonal expansion of, and cognate destruction by CD8(+) T lymphocytes in vivo.

Knockdown of lncRNA XIST inhibits hypoxia-induced glycolysis, migration and invasion through regulating miR-381-3p/NEK5 axis in nasopharyngeal carcinoma.

OBJECTIVE: Hypoxia is an important feature of nasopharyngeal carcinoma (NPC). Growing evidence demonstrated that long non-coding RNAs (lncRNAs) could participate in cancer progression and hypoxia regulation. However, the exact roles and underlying mechanism of lncRNA X-inactive specific transcript (XIST) in NPC under hypoxia are still unclear. MATERIALS AND METHODS: The expressions of XIST, microRNA-381-3p (miR-381-3p) and NIMA related kinase 5 (NEK5) were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The glucose consumption and lactate production were measured using the glucose assay kit and lactate assay kit, respectively. Western blot assay was used to determine the protein levels of hexokinase II (HK2) and NEK5. Transwell assay was employed to evaluate cell migration and invasion. The interaction between miR-381-3p and XIST or NEK5 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. The mice xenograft model was established to investigate the roles of XIST in NPC progression in vivo. RESULTS: XIST and NEK5 were highly expressed while miR-381-3p was lowly expressed in NPC (tissues and cells) and hypoxia-induced NPC cells. Deficiency of XIST or NEK5 suppressed hypoxia-induced glycolysis and metastasis in NPC cells. Moreover, miR-381-3p could directly bind to XIST and its inhibition reversed the inhibitory effects of XIST knockdown on glycolysis and metastasis under hypoxia. NEK5 was a direct target of miR-381-3p and its interference attenuated the promotive effects of miR-381-3p downregulation on glycolysis and metastasis under hypoxic conditions. Besides, interference of XIST decreased tumor growth by upregulating miR-381-3p and downregulating NEK5. CONCLUSIONS: XIST knockdown inhibited glycolysis and metastasis in hypoxia-induced NPC cells through regulating miR-381-3p/NEK5 axis, providing new insights into the pathogenesis of NPC.

[Clinical research of extensive alveolar cleft treatment with computer assistant distraction osteogenesis].

Objective: To evaluate the feasibility and outcome of computer assisted distraction osteogenesis in the treatment of extensive alveolar cleft. Methods: Four patients [1 male and 3 females, aged (15.5±3.7) years] received treatment in the Department of Oral-Maxillofacial Surgery and Plastic Surgery, School of Stomatology, China Medical University from June 2016 to April 2018 were involved in this study. All the patients with extensive alveolar cleft [cleft width (7.64±1.29) mm] were performed orthodontic treatment to expand the dental arch and interdental space between the first molar and premolars. Three-dimensional (3D) model of the maxilla and the osteotomy guider were printed according to the CT data. The fix wings of the distractor were pre-shaped according to the 3D model. The osteotomy was performed at the interdental space and horizontal plate of palate to dissociate the alveolar bone segment. The distractor was fixed on the predetermined position. Distraction (0.4-0.8 mm/day) was performed in 7 days later and stopped when the incision connected with the canine. The distractor was removed after six months. Results: The distraction period was (10.8±2.5) d in four cases. The cleft was completely closed with interdental bone anchored distraction in four cases. The imaging examination in six months showed good new bone structure in the distraction zone and bone connection of the cleft. Conclusions: Computer assisted distraction osteogenesis was effective and feasible to close the extensive alveolar cleft and provide sufficient new bone tissue.

IL-21 modulates CD4+ CD25+ regulatory T-cell homeostasis in experimental autoimmune encephalomyelitis.

The homeostasis of CD4+ CD25+ regulatory T cells (Tregs) depends on the cytokine interleukin (IL)-2. As IL-21 shares sequence homology with IL-2 and the IL-21 receptors contain a gamma-chain common to IL-2, we hypothesized that IL-21 could also affect the homeostasis of Tregs. We tested this hypothesis in experimental autoimmune encephalomyelitis (EAE), an animal model of relapsing-remitting human multiple sclerosis. We show that blockade of IL-21 in SJL/J mice before and after the induction of EAE enhances the influx of inflammatory cells into the central nervous system (CNS). The blockade of IL-21 leads to proliferation of proteolipid peptide (PLP(139-151))-autoreactive CD4+ T cells, which are capable to cause severe EAE in adoptively transferred recipient mice. Conversely, Tregs from mice where IL-21 was blocked, lose their capacity to prevent EAE induced PLP(139-151)-reactive T cells. Notably, direct effects of IL-21 on Tregs are confirmed by studies of blockade of IL-21 in mice expressing a green fluorescent protein 'knocked' into a Foxp3 allele, in which a reduction of the number of Tregs and a downregulation of their frequency and expression of Foxp3 are observed. These data suggest a role of the IL-21/IL-21R axis in the homeostasis of Tregs in CNS autoimmunity.

In vitro hepatic differentiation of mesenchymal stem cells from human fetal bone marrow.

We examined whether human fetal mesenchymal stem cells (FMSCs) derived from fetal bone marrow were able to differentiate into functional hepatocyte-like cells in vitro. The surface phenotype of FMSCs was characterized by flow cytometry. To induce hepatic differentiation of FMSCs, we added hepatocyte growth factor, basic fibroblast growth factor and oncostatin M into the cell culture medium. After 21 days of hepatocyte induction, FMSCs expressed the hepatocyte-specific markers, alpha-fetoprotein and cytokeratin 18, as demonstrated by immunofluorescence staining. Differentiated FMSCs also demonstrated in vitro functions characteristic of liver cells, including albumin production, urea secretion and glycogen storage. In conclusion, fetal bone marrow-derived FMSCs are able to differentiate into functional hepatocytelike cells and may serve as a source of cells for liver disease therapy.

The heat-stable antigen determines pathogenicity of self-reactive T cells in experimental autoimmune encephalomyelitis.

Induction of myelin-specific CD4 T cells is a pivotal event in the development of experimental autoimmune encephalomyelitis (EAE). Other checkpoints in EAE pathogenesis have not been clearly defined, although multiple genetic loci are known to influence EAE development. We report here that targeted mutation of the heat-stable antigen (HSA) abrogates development of EAE despite a complete lack of effect on induction of autoimmune T cells. To test whether T-cell expression of HSA is sufficient, we created transgenic mice in which HSA is expressed exclusively in the T-cell lineage. We found that these mice remain resistant to EAE induction. Adoptive transfer studies demonstrate that both T cells and non-T cells must express HSA in order for the pathogenic T cells to execute their effector function. Moreover, HSAIg, a fusion protein consisting of the extracellular domain of the HSA and the Fc portion of immunoglobulin, drastically ameliorates the clinical sign of EAE even when administrated after self-reactive T cells had been expanded. Thus, identification of HSA as a novel checkpoint, even after activation and expansion of self-reactive T cells, provides a novel approach for immunotherapy of autoimmune neurologic diseases, such as multiple sclerosis.

Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

Optimal induction of effector but not memory antitumor cytotoxic T lymphocytes involves direct antigen presentation by the tumor cells.

MHC class I-restricted tumor antigen can be presented to CD8+ T cells by two distinct mechanisms. Direct presentation involves degradation of cytosolic proteins by the proteosome into peptides, transport of the peptides across the endoplasmic reticulum membrane, and expression of the MHC-peptide complex on the tumor cell surface. Cross-presentation, on the other hand, involves uptake and intracellular processing of the tumor antigen by host antigen-presenting cells. Whereas it is clear that cross-presentation is necessary and sufficient for the induction of memory CTLs, it has not been tested whether such presentation is sufficient to induce effector CTLs. Here we analyzed the requirements of direct antigen presentation for the induction of effector and memory antitumor CTLs using a MHC class I- mutant incapable of direct antigen presentation and its parent, the MHC class I+ J558 cell line. We report that in comparison with the MHC class I+ tumor cell, the MHC class I- mutant induces equal priming for recall CTL response but poor effector CTLs. Our results demonstrate that optimal induction of effector CTLs, but not memory CTLs, requires direct antigen presentation by the tumor cells.

On the site and mode of antigen presentation for the initiation of clonal expansion of CD8 T cells specific for a natural tumor antigen.

Because of the low frequency of antigen-specific T cells, early events in the activation of tumor-specific T cells in vivo have not been well characterized. There is still no direct documentation on where the clonal expansion begins and how tumor antigens are presented to the host CD8 T cells to initiate it. Here we used transgenic T cells specific for a natural tumor antigen P1A to evaluate the kinetics, location, and modes of antigen presentation for initiating CTL response in vivo. Our results demonstrate that the initial activation of P1A-specific T cells takes place in the lymphoid organs. The activated T cells then migrate into tumors, where they undergo accelerated division and acquire distinct activation markers. The site of initiation cannot be altered by either local expression of costimulatory molecules or by intratumor injection of naïve T cells. Moreover, using genetic models that allow only one mode of antigen presentation, we show here that both cross-presentation of P1A by the host antigen-presenting cells, and direct antigen presentation and costimulation by the tumor cells are sufficient to initiate rapid T cell-clonal expansion in the lymphoid organ. These results provide direct evidence for two fundamental assumptions on the mechanisms of T-cell activation in vivo.

The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer.

AIM: Serum tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and CA242 were investigated to evaluate the values of single and combined test in the diagnosis and prognosis of pancreatic cancer. METHODS: Pre-operative serum CEA, CA19-9 and CA242 were measured in 105 pancreatic cancers, 70 non-pancreatic malignancies and 30 benign pancreatic diseases. RESULTS: The sensitivity of CA19-9 alone was the highest in pancreatic cancer patients (80%), but the specificity was significantly lower than that of CEA and CA242 (P<0.01). The combination of CEA and CA242 could increase the specificity to 92%. In serum CA242 positive patients, the survival time was remarkably shorter than that of patients with negative result (P<0.01). The survival time in patients with more than two markers positive expression of CEA, CA19-9 and CA242 was obviously shorter than that of only one or no marker positive expression (P<0.05). CONCLUSION: The diagnostic rate of CA19-9 in pancreatic cancer is better than that of CEA and CA242. Combined detection of CEA and CA242 can improve the diagnostic specificity obviously. High levels of serum markers are associated with advanced stage of the disease. Patients with two or three markers positive expression of CEA, CA19-9, and CA242 simultaneously had a shorter survival time.

Experimental allergic neuritis: cytolysin mRNA expression is upregulated in lymph node cells during convalescence.

Experimental allergic neuritis (EAN) is a T cell mediated animal model of Guillain-Barré syndrome, characterized by inflammation and demyelination of the peripheral nervous system (PNS). To study the involvement of immunoregulatory cytokines, we induced EAN in Lewis rats by immunizing with bovine PNS myelin (BPM) and Freund's complete adjuvant. mRNA expression of the cytokines IL-1beta, IL-6, IL-10, IL-12, TNF-alpha and TNF-beta, and the cytolytic effector molecule cytolysin was examined in lymph node mononuclear cells (MNC) over the course of EAN by in situ hybridization after culture without antigen and in the presence of BPM, the myelin P2 protein, the control antigen acetylcholine receptor, or the mitogen PHA. Three patterns of cytokine mRNA expressing MNC in relation to clinical EAN could be distinguished: (i) IL-1beta mRNA expressing cells peaked already on day 3 post immunization (p.i.), and BPM- and P2-reactive TNF-alpha, and BPM-reactive IL-6 mRNA expressing cells were also detected already on day 7 p.i., i.e., before onset of clinical EAN; (ii) BPM- and P2-reactive TNF-alpha peaked together with P2-reactive TNF-beta, IL-6 and IL-12 mRNA expressing cells at height of clinical EAN, consistent with a disease-promoting role for these four cytokines; (iii) high levels of BPM- and P2-reactive IL-10 and cytolysin mRNA expressing cells were observed only during recovery (day 28 p.i.), consistent with a disease down-regulating role of IL-10 and cytolysin. The results suggest a major proinflammatory role for IL-1beta, TNF-alpha, TNF-beta, IL-6 and IL-12 and a disease down-regulating function of IL-10 as well as cytolysin in EAN.

Suppression of acute and protracted-relapsing experimental allergic encephalomyelitis by nasal administration of low-dose IL-10 in rats.

In this study we report for the first time that nasal administration of the Th2 cell-related cytokine interleukin-10 (IL-10), at concentrations of 1.5 microg/rat and 15 microg/rat, suppressed clinical signs of acute experimental allergic encephalomyelitis (EAE) in Lewis rats and prevented the development and relapse of protracted-relapsing EAE (PR-EAE) in DA rats. In contrast, subcutaneous injection of IL-10 (15 microg/rat) did not inhibit acute EAE. The IL-10-mediated suppression of EAE was associated with decreased myelin antigen-specific T-cell proliferative responses and IFN-gamma secretion in both acute and PR-EAE. In sections of spinal cords derived from rats nasally pretreated with IL-10, there were no infiltrating CD4+ T cells or macrophages, which are considered as major encephalitogenic or inflammatory cells. Most interestingly, nasally administered IL-10 also inhibited MHC class II expression in microglia, indicating that IL-10 administration by the nasal route prevents the activation of microglia. Administration of cytokines via the nasal route offers an exciting alternative in the prevention and treatment of autoimmune diseases.