Th1-like Cytokine Research Articles

In vitro characterization of chicken bone marrow-derived dendritic cells following infection with very virulent infectious bursal disease virus

Infectious bursal disease is caused by infectious bursal disease virus (IBDV), an immunosuppressive virus that targets immune cells such as B cells and macrophages. However, the involvement of dendritic cells (DCs) during IBDV infection is not well understood. In this study the in vitro effects of live and inactivated very virulent IBDV (vvIBDV) UPM0081 on bone marrow-derived DCs (BM-DC) were characterized and compared with BM-DC treated with lipopolysaccharide (LPS). Morphologically, BM-DC treated with LPS and vvIBDV showed stellate shape when compared to immature BM-DC. In addition, LPS-treated and both live and inactivated vvIBDV-infected BM-DC expressed high levels of double positive CD86 and major histocompatibility complex class II antigens (>20%). vvIBDV-infected BM-DC showed significantly higher numbers of apoptotic cells compared to LPS. Replication of vvIBDV was detected in the infected BM-DC as evidenced by the increased expression of VP3 and VP4 IBDV antigens based on flow cytometry, real-time polymerase chain reaction and immunofluorescence tests. Levels of different immune-related genes such as interleukin-1β (IL-1β), CXCLi2 (IL-8), IL-18, interferon gamma (IFN-γ, IL-12α, CCR7 and Toll-like receptor-3 (TLR3) were measured after LPS and vvIBDV treatments. However, marked differences were noticed in the onset and intensity of the gene expression between these two treatment groups. LPS was far more potent than live and inactivated vvIBDV in inducing the expression of IL-1β, IL-18 and CCR7 while expression of Th1-like cytokines, IFN-γ and IL-12α were significantly increased in the live vvIBDV treatment group. Meanwhile, the expression of TLR3 was increased in live vvIBDV-infected BM-DC as compared to control. Inactivated vvIBDV-treated BM-DC failed to stimulate IFN-γ, IL-12α and TLR3 expressions. This study suggested that BM-DC may serve as another target cells during IBDV infection which require further confirmation via in vivo studies.

Sexual activity modulates shifts in TH1/TH2 cytokine profile across the menstrual cycle: an observational study

To investigate if sexual activity moderated menstrual cycle-related shifts in cytokines associated with T-helper type 1 (TH1) cells (e.g., interferon [IFN] γ) and T-helper type 2 (TH2) cells (e.g., interleukin [IL] 4). Immune activity shifts across the menstrual cycle, with higher follicular-phase TH1-cell activity but higher luteal-phase TH2-cell activity. Little is known about how social behaviors alter TH1-TH2 ratios, despite evidence that psychosocial factors can influence immunity. Of particular interest is how sexual activity influences immune responses that may support conception, such as the TH1-TH2 balance. Participants provided saliva samples at four time points (menstrual, follicular, ovulatory, and luteal phases), which were assayed by means of ELISA. Academic laboratory. Thirty healthy premenopausal women (16 sexually abstinent, 14 sexually active) not taking hormonal or immunoactive medications. None. Salivary E2, P, IFN-γ, and IL-4. Sexually active, but not abstinent, women were significantly more likely to express TH2-like cytokine ratios (IFN-γ < IL-4) in the luteal phase than in other phases. Similarly, sexually active women had significantly higher P, and higher P-E2 ratios, in the luteal phase than did abstinent women. The P-E2 ratio mediated menstrual variations in cytokine ratios in sexually active women. These results support the hypothesis that shifts in immune response across the menstrual cycle may reflect tradeoffs between reproduction and immunity. These findings point to the need for further research on the interaction between sexual behavior, the menstrual cycle, and immune response.

Ingested (oral) tocilizumab inhibits EAE

BackgroundBlocking the activity of IL-6 can inhibit autoimmune diseases such as rheumatoid arthritis and Crohn’s disease. ObjectiveWe examined whether an antibody against IL-6, tocilizumab (TCZ) (Actemra®), used clinically in rheumatoid arthritis (RA) would have similar anti-inflammatory effects in EAE after oral administration. Design/methodB6 mice were immunized with MOG peptide 35–55 and gavaged with control saline or TCZ during ongoing disease. Splenocytes, CD4+ T cells or macrophages/monocyte lineage cells (CD11b+) from control fed or TCZ fed mice were adoptively transferred into active MOG peptide 35–55 immunized recipient mice during ongoing disease. Actively fed and recipient mice were examined for disease inhibition, inflammation, and cytokine responses. ResultsIngested (oral) TCZ inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from TCZ fed donors protected against actively induced disease and decreased inflammation. There was a decrease in IL-6 in actively treated spleen, decrease in TNF-α, Th1-like cytokine IL-12 and increase in Th2-like cytokine IL-10 in active fed and adoptively treated recipients. ConclusionsIngested (orally administered) TCZ can inhibit disease, CNS inflammation, decrease pro-inflammatory Th1-like cytokines and increase Th2-like anti-inflammatory cytokines.

Respiratory syncytial virus‐induced chronic airway inflammation and AHR (CAI‐CAHR) is associated with upregulation of Th2‐like cytokines via TLRs‐TRIF but not TSLP signaling pathway (870.2)

We have shown that TLRs‐TRIF pathway is responsible for the RSV infection‐induced CAI‐CAHR. This pathway is reportedly involved in Th2 responses that are predominate in the patients with severe RSV infection. Thus, we hypothesized that the RSV‐induced CAI‐CAHR was associated with upregulation of Th2‐like cytokines dependent on TLRs‐TRIF pathway. Mice at day 7, 14, 21, 30 and 60 postinfection were placed in a whole body plethysmograph to define AHR or euthanized to determine Th2‐like cytokines (in BALF) and airway inflammation (inflammatory cells in BALF and histopathology). RSV infection induced CAI‐CAHR concomitant with significant (All P &lt; 0.05 or 0.01) elevation of IL‐4, IL‐5, IL‐10, IL‐13, TNF‐α and TSLP from day 14 to 60 postinfection with the peak at day 21. The same protocols were performed in other mice after giving resveratrol (inhibitor of TRIF, ip) daily from day 0 to day 21 postinfection. Resveratrol treatment strikingly reduced the RSV infection‐induced Th2‐like cytokines and CAI‐CAHR. As Th2‐like cytokines are also controlled by TSLP in asthmatic patients and animals, anti‐TSLP neutralized antibody (ip, on day 14 after postinfection) was utilized in the subsequent study. This treatment failed to alter the peak Th2‐like cytokines and CAI‐CAHR. Our results suggest that RSV infection‐induced CAI‐CAHR is associated with upregulation of Th2‐like cytokines via TLRs‐TRIF but not TSLP signaling pathway.

Altered Invariant Natural Killer T cell Subsets and its Functions in Patients with Oral Squamous Cell Carcinoma

Invariant natural killer T (iNKT) cells are glycolipid-reactive T lymphocytes that share receptors and function with natural killer (NK) cells and reportedly play a pivotal role in various immune responses. However, iNKT cells are not well characterized in patients with oral squamous cell carcinoma (OSCC). We investigated the populations and functions of circulating iNKT (CD3(+) 6B11(+) ) cells from thirty-eight patients with OSCC and twenty-eight healthy donors by flow cytometry. Circulating iNKT cells were significantly lower (P < 0.01) in patients as compared to those in healthy controls. Further, iNKT subsets revealed a marked decrease in CD4(-) CD8(-) (double negative, DN) subset with concomitant increase in CD8(+) subset in patients as compared to healthy controls (P = 0.03 and P < 0.01, respectively), whereas CD4(+) subset was similarly distributed in both groups. The functional analysis demonstrated that residual iNKT cells from patients had impaired proliferative response to α-galactosylceramide (α-GalCer)-pulsed dendritic cells (DCs) and Th2-like cytokine profile. However, in vitro activation with α-GalCer-pulsed DCs restores IFN-γ expression and enhances antitumour activity to human cancer cells lines (SCC-4, KB and MCF7). It appears that the selectively enriched iNKT subsets and modulation of their function by specific ligand/agonist may be useful for cellular therapy in patients with OSCC. Further, reduced levels of iNKT cells and its DN subset may be used as potential prognostic factors for patients with OSCC.

Plasma cytokine levels and human papillomavirus infection at the cervix in rural Nigerian women

IntroductionWe conducted a study to test the hypothesis that systemic dysregulation of Th1/Th2 cytokine levels was associated with detection of carcinogenic or overall human papillomavirus (HPV) at the cervix among 964 women residing in a rural village in Nigeria. MethodsLevels in plasma were measured for 19 cytokines, including Th1-like cytokines IL-2, IL-12 (p40), TNF-a, IFN-g; Th2-like cytokines IL-4, IL-5, IL-6, IL-10, IL-13; innate/inflammation cytokines IL-1a, IL-1b, IL-8, eotaxin, MCP-1, MIP-1a, and IL-7; and cell development cytokines G-CSF, VEGF, and IL-17. Analysis was restricted to 5 cytokines, TNF-α (Th1), IL-8 (Th2), eotaxin and MCP-1 (innate/inflammation), and G-CSF (cell development), whose levels were detected in 80% or more of the samples measured as well as had a coefficient of variation of <30%. ResultsStrong correlations were noted between levels of eotaxin and TNF-α (r=0.75), IL-8 and MCP-1 (r=0.60), eotaxin and G-CSF (r=0.44), and G-CSF and IFN-γ (r=0.43). Detection of carcinogenic or non-carcinogenic HPV DNA was unrelated to cytokine levels, except for levels of eotaxin and TNF-α, which were inversely correlated, albeit weakly, with detection of any carcinogenic HPV (P=0.048 and P=0.067, respectively). In analyses stratified by age group, levels of eotaxin were inversely correlated with detection of any HPV DNA (P=0.026) and carcinogenic HPV (P=0.042) in older, but not younger, women. ConclusionsOur results do not support the hypothesis of association between systemic cytokine dysregulation and detection of HPV at the cervix in Nigerian women, but subgroup analyses raise questions about inverse associations between eotaxin and TNF-α in older women.

IL-4 induces a suppressive IL-10-producing CD8+ T cell population via a Cdkn2a-dependent mechanism

IL‐4 induced IL‐10‐producing CD8+ T cells possess suppressive function both in vitro and in vivo.

1087 THERAPEUTIC EFFECT OF S-ADENOSYLMETHIONINE ON LIVER TUMOR DEVELOPMENT IN MURINE INFLAMMATION-MEDIATED MODEL IS ASSOCIATED WITH INCREASED EXPRESSION OF TUMOR SUPPRESSOR GENES AND CELL CYCLE ARREST

suppressors of anti-tumor immunity at the tumor site of patients with liver cancer. Now, we observed that in addition to Treg, tumor-infiltrating lymphocytes (TILs) contain a subset of CD4+ T cells that is concentrated at the tumor site, produces IL-10, and does not express FoxP3. These cells do not produce the Th2-like cytokine IL-13, but the majority can produce IFNg. Tumor-derived IL-10 producing CD4+ T cells have a potent capacity to suppress proliferation and cytokine production by autologous and allogenic effector T cells. These results indicate for the first time to our knowledge that besides CD4+FoxP3+ Tregs, liver tumors contain another subset of CD4+ T cells that is able to suppress the local immune response. It’s phenotype and function resemble that of type 1 regulatory T (Tr1) cells, and it may also interfere with immunotherapeutic efforts designed to treat patients with liver cancer.

Induction of chicken cytokine responses in vivo and in vitro by lipooligosaccharide of Campylobacter jejuni HS:10

Campylobacter jejuni is a pathogen of the gastrointestinal tract of humans, but colonizes chickens for prolonged periods without causing disease. It is unclear what host and bacterial mechanisms maintain a non-inflammatory state in chickens. The present work was undertaken to characterize cytokine responses of chickens to purified lipooligosaccharide (LOS) of C. jejuni HS:10. Chickens were injected with purified LOS, and expression of interleukin (IL)-1β (pro-inflammatory cytokine), IL-8 (pro-inflammatory chemokine), interferon (IFN)γ (Th1-like cytokine), IL-10 (immune regulatory/anti-inflammatory cytokine) and IL-13 (Th2-like cytokine) was evaluated in spleen using quantitative RT-PCR, up to 24h post-injection. In an in vitro study, splenocytes were incubated with LOS, and cytokine expression followed up to 18 h. Chickens injected with LOS had increased expression of IL-1β up to 24h later. Expression of IL-8 was significantly increased at 2h but then declined below baseline. Expression of IFNγ and IL-10 was increased significantly at 2h, but declined thereafter. Splenocytes incubated with LOS had increased expression of IL-1β and IL-8 up to 18 h of incubation. Expression of IFNγ was increased at 6 and 18 h, IL-10 was increased at 2h, but expression of IL-13 did not differ significantly up to 18h. It is concluded that LOS of C. jejuni can induce expression of pro-inflammatory IL-1β and IL-8, as well as IFNγ and IL-10 in chickens. More extensive studies with more prolonged exposure to LOS are needed to further clarify the interaction between C. jejuni and the chicken host.

Th1 and Th2-like Protein Balance in Human Inflammatory Radicular Cysts and Periapical Granulomas

IntroductionChronic dental periapical lesions result from chronic inflammation of periapical tissues caused by continuous antigenic stimulation from infected root canals. Recent findings have suggested that T helper (Th) 1 and Th2-like cytokines are important in the pathogenesis of chronic periapical inflammatory diseases. However, the mechanisms regulating these immunoinflammatory pathways have not been fully elucidated. Thus, the aim of this study was to evaluate interleukin (IL)-4, IL-12, and interferon γ (IFN-γ) protein levels in human radicular cysts and periapical granulomas. MethodsArchived samples of cysts (n = 52) and granulomas (n = 27) were sectioned and submitted to immunohistochemistry to evaluate the tissue expression of IL-4, IL-12, and IFN-γ. The data were analyzed using the Mann-Whitney U test (P < .05). ResultsAn increased expression of IFN-γ was observed in radicular cysts. IL-4 expression was stronger in periapical granulomas than in radicular cysts. IL-12 was not detected in any of the samples. ConclusionsOur study showed that IFN-γ protein levels are increased in radicular cysts, whereas IL-4 expression is stronger in samples of periapical granulomas. Further studies are necessary to elucidate the signaling pathways mediated by these cytokines and to facilitate the development of more effective periapical disease management strategies.

Respiratory syncytial virus protects against the subsequent development of ovalbumin‐induced allergic responses by inhibiting Th2‐type γδ T cells

Respiratory syncytial virus (RSV) infection has been hypothesized to be a risk factor for the development of allergy and asthma, but epidemiologic studies in humans still remain inconclusive. The association between RSV infection and allergic diseases may be dependent on an atopic background and previous history of RSV infection. It has been reported that RSV infection before sensitization to an allergen decreased the production of Th2-like cytokines in the lung and the levels of allergen-specific Th2-type antibodies in the serum. However, the underlying mechanisms are largely unknown. In the present study, the role of pulmonary γδ T cells in RSV-affected, allergen-induced airway inflammation was investigated. BALB/c mice were sensitized to or challenged with ovalbumin (OVA) and infected with RSV either before or after the sensitization period. It became clear that sensitization and challenge of mice with OVA induced a large influx of γδ T cells to the lungs. However, prior RSV infection inhibited the infiltration of γδ T cells as well as activated γδ T cells, characterized by expression of CD40L or CD69 molecular in the cell surface. Moreover, prior RSV infection elevated the type 1 cytokine gene expression but suppressed type 2 cytokine expression in the lung γδ T cells. Adoptive transfer of γδ T cells from OVA-sensitized and challenged mice increased airway inflammation, suggesting that γδ T cells may play a proinflammatory role in allergic responses. These results described here support the idea of an unknown γδ T cell-dependent mechanism in the regulation of RSV-affected, allergen-induced allergic airway responses.

Ingested (oral) thyrotropin releasing factor (TRH) inhibits EAE

BackgroundIngested immunoactive proteins type I IFN, SIRS peptide 1–21, α-MSH, ACTH, SST inhibit clinical attacks and inflammation in acute EAE by decreasing Th1-like cytokines, increasing Th2-like cytokines or increasing Treg cell frequencies. ObjectiveWe examined whether another protein, thyrotropin releasing factor (TRH), would have similar anti-inflammatory effects in EAE after oral administration. Design/methodsB6 mice were immunized with MOG peptide 35–55 and gavaged with control saline or TRH during ongoing disease. Splenocytes from mock fed or TRH fed mice were adoptively transferred into active MOG peptide 35–55 immunized recipient mice during ongoing disease. ResultsIngested (oral) TRH inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from TRH fed donors protected against actively induced disease and decreased inflammation. In actively fed mice, oral TRH decreased IL-17 and TNF-α cytokines in both the spleen and the CNS. In recipients of donor cells from TRH fed mice there was a reduction of Th1 and Th17 and induction of Th2-like IL-13 cytokines in both the spleen and CNS. Oral TRH decreased clinical score and decreased inflammatory foci in both actively fed and recipients of actively fed mice. There was no significant increase in Treg cell frequencies in actively fed or recipients of TRH fed donor cells. ConclusionsIngested (orally administered) TRH can inhibit clinical disease, inhibit CNS inflammation by decreasing Th1-like, Th17 and TNF-α cytokines and increasing Th2-like cytokines (IL-13) in the CNS.

CD4+ T Lymphocytes, Especially Th2 Cells, Contribute to the Progress of Renal Fibrosis

Background: Renal tubulointerstitial fibrosis is the final common stage of renal failure. CD4+ T lymphocyte recruitment and activation after injury could be the very important early event that mediates the onset of renal fibrogenesis. But the role of CD4+ T lymphocytes in renal fibrosis is controversial and its cellular mechanism needs to be further investigated. Methods: Biopsy specimens were from patients with minimal-change or IgA nephropathy. Mouse renal fibrosis was induced by unilateral ureteral obstruction (UUO). CD4+ T lymphocytes of wild BALB/c mice were depleted with anti-CD4 antibody. BALB/c Nu/Nu mice were reconstituted with polarized Th1 or Th2 cells by tail vein injection. Results: Our study demonstrated that massive CD4+ T lymphocytes infiltrated fibrotic kidneys of patients. The depletion of CD4+ T lymphocytes inhibited UUO-induced mouse renal fibrosis. In the process of UUO-induced renal fibrosis, the ratios of Th2/Th1 increased with time. Results have also shown that Th2-reconstituted mice developed renal fibrosis more easily than Th1-reconstituted mice, which manifested by interstitial expansion and collagen deposition, higher expression of α-SMA and vimentin and increased expression of fibronectin, TGF-β and collagen I. We also found that CD4+ T cells from Th1-reconstitued mice tended to secrete IL-4 and IL-13 Th2-like cytokines. Conclusion: In conclusion, our study demonstrated the importance of CD4+ T lymphocytes in renal fibrosis and gave the first direct evidence that Th2 cells play a pivotal role in UUO-induced renal fibrosis. Inhibition of CD4+ T lymphocyte differentiation to Th2 would be a potential therapeutic intervention to prevent renal fibrosis.

Optimisation of prime-boost immunization in mice using novel protein-based and recombinant vaccinia (Tiantan)-based HBV vaccine.

BackgroundA therapeutic vaccine for chronic hepatitis B virus (HBV) infection that enhances virus-specific cellular immune responses is urgently needed. The “prime–boost” regimen is a widely used vaccine strategy against many persistence infections. However, few reports have addressed this strategy applying for HBV therapeutic vaccine development.Methodology/Principal FindingsTo develop an effective HBV therapeutic vaccine, we constructed a recombinant vaccinia virus (Tiantan) containing the S+PreS1 fusion antigen (RVJSS1) combined with the HBV particle-like subunit vaccine HBVSS1 to explore the most effective prime–boost regimen against HBV. The immune responses to different prime–boost regimens were assessed in C57BL/C mice by ELISA, ELISpot assay and Intracellular cytokine staining analysis. Among the combinations tested, an HBV protein particle vaccine priming and recombinant vaccinia virus boosting strategy accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody) titres as well as the strongest multi-antigen (PreS1, and S)-specific cellular immune response. HBSS1 protein prime/RVJSS1 boost immunization was also generated more significant level of both CD4+ and CD8+ T cell responses for Th1 cytokines (TNF-α and IFN-γ).ConclusionsThe HBSS1 protein-vaccine prime plus RVJSS1 vector boost elicits specific antibody as well as CD4 and CD8 cells secreting Th1-like cytokines, and these immune responses may be important parameters for the future HBV therapeutic vaccines.

Neonatal levels of cytokines and risk of autism spectrum disorders: An exploratory register-based historic birth cohort study utilizing the Danish Newborn Screening Biobank

The aim of the study was to analyze cytokine profiles in neonatal dried blood samples (n-DBSS) retrieved from The Danish Newborn Screening Biobank of children developing Autism Spectrum Disorders (ASD) later in life and controls. Samples of 359 ASD cases and 741 controls were analyzed using Luminex xMAP technology and clinical data were retrieved from nationwide registers. Findings showed that children developing ASD were more likely to have decreased levels of both T helper-1(Th-1)-like cytokines (i.e. IFN-γ) and Th-2like cytokines (i.e. IL-4, IL-10) which may suggest a depressed or hypoactive immune cell activity during neonatal period in ASD.

Ingested (oral) neuropeptide Y inhibits EAE

BackgroundIngested immunoactive proteins, type I IFN, SIRS peptide 1–21, α-MSH, ACTH, and SST inhibit clinical attacks and inflammation in acute EAE by decreasing Th1-like cytokines, increasing Th2-like cytokines or increasing Treg cell frequencies. ObjectiveWe examined whether another protein, neuropeptide Y, would have similar anti-inflammatory effects in EAE after oral administration. Design/methodsB6 mice were immunized with MOG peptide 35–55 and gavaged with control saline or NPY during ongoing disease. Splenocytes from mock fed or NPY fed mice were adoptively transferred into active MOG peptide 35–55 immunized recipient mice during ongoing disease. ResultsIngested (oral) NPY inhibited ongoing disease, and decreased inflammation. Adoptively transferred cells from NPY fed donors protected against actively induced disease and decreased inflammation. In actively fed mice, oral NPY decreased Th1-like cytokines and increased Th2-like IL-13 cytokines in both the spleen and the CNS. In recipients of donor cells from NPY fed mice there was a reduction of Th1 and Th17 and induction of Th2-like IL-13 cytokines in both the spleen and CNS. Oral NPY decreased clinical score and decreased inflammatory foci in both actively fed and recipients of actively fed mice. There was no significant increase in Treg cell frequencies in actively fed or recipients of NPY fed donor cells. ConclusionsIngested (orally administered) NPY can inhibit clinical disease, inhibit CNS inflammation by decreasing Th17 and Th1-like cytokines and increasing Th2-like cytokines in the CNS.

Polyinosinic-Polycytidylic Acid Limits Tumor Outgrowth in a Mouse Model of Metastatic Lung Cancer

Polyinosinic-polycytidylic acid (poly I:C), a TLR3 ligand, is currently being tested in human clinical trials as an adjuvant to anti-cancer vaccines and in combination with other therapies. However, little is known about its activity in established pulmonary metastasis. The aim of our study was to elucidate the effect of poly I:C (1, 10, or 100 μg/mouse) in a mouse model of B16-F10-induced metastatic lung cancer. Lung tumor growth was arrested after a single administration of poly I:C. This was associated with higher influx of mature dendritic cells (DCs), which drove toward a Th1-like, Th17-like, and cytotoxic immune environment. The interference with IFN type I receptor signaling by means of a specific mAb reversed poly I:C-mediated tumor regression due to lower presence of myeloid DCs, cytotoxic DCs (CD11c(+)CD8(+)), NKT cells, CD8(+) T cells, and Th1-like cytokines. Moreover, the adoptive transfer of poly I:C-activated bone marrow-derived DCs into tumor-bearing mice resulted in activities similar to those of the systemic administration of poly I:C on lung tumor burden. In conclusion, our data prove that poly I:C has potential anti-tumor activity in a mouse model of established pulmonary metastasis. The activation of DCs and the production of IFN type I are responsible for an effective T cytotoxic immune response against metastatic lung cancer progression after poly I:C treatment.

Studies on the biological function of virus-like particles of foot and mouth disease (160.13)

Abstract Foot and mouth disease (FMD), a severe and highly contagious viral disease of cloven-hoofed animals, is the most economically devastating livestock disease in the world. The development of a cheap and noninfectious virus-like particle (VLP) vaccine has now attracted worldwide interest. In this study, we used SUMO fusion technology to produce a VLP of FMD virus (FMDV). The purified FMD-VLPs morphologically resembled FMD virions and were able to interact with host receptors in a manner similar to FMDV. Immunization of guinea pig or swine with FMD-VLPs resulted in the production of anti-FMDV neutralizing antibodies. RT-PCR analysis of peripheral blood mononuclear cells (PBMC) from the FMD-VLPs-immunized swine revealed that FMD-VLPs enhanced the transcription of Th1-like cytokines (IFN- and IL-2) and Th2-like cytokines (IL-4 and IL-10). Further investigation of the immune mechanisms revealed that FMD-VLPs induced maturation of dendritic cells (DCs) via toll-like receptors 2 (TLR2) to induce CD4+ and CD8+ T proliferation. These results suggest that FMD-VLPs could be used as an effective vaccine candidate against FMDV.

Improved immune responses against avian influenza virus following oral vaccination of chickens with HA DNA vaccine using attenuated Salmonella typhimurium as carrier

This study evaluates the immune responses of single avian influenza virus (AIV) HA DNA vaccine immunization using attenuated Salmonella enterica sv. Typhimurium as an oral vaccine carrier and intramuscular (IM) DNA injection. One-day-old specific-pathogen-free (SPF) chicks immunized once by oral gavage with 10(9) Salmonella colony-forming units containing plasmid expression vector encoding the HA gene of A/Ck/Malaysia/5858/04 (H5N1) (pcDNA3.1.H5) did not show any clinical manifestations. Serum hemagglutination inhibition (HI) titer samples collected from the IM immunized chickens were low compared to those immunized with S. typhimurium.pcDNA3.1.H5. The highest average antibody titers were detected on day 35 post immunization for both IM and S. typhimurium.pcDNA3.1.H5 immunized groups, at 4.0±2.8 and 51.2±7.5, respectively. S. typhimurium.pcDNA3.1.H5 also elicited both CD4(+) and CD8(+) T cells from peripheral blood mononuclear cells (PBMCs) of immunized chickens as early as day 14 after immunization, at 20.5±2.0 and 22.9±1.9%, respectively. Meanwhile, the CD4(+) and CD8(+) T cells in chickens vaccinated intramuscularly were low at 5.9±0.9 and 8.5±1.3%, respectively. Immunization of chickens with S. typhimurium.pcDNA3.1.H5 enhanced IL-1β, IL-12β, IL-15 and IL-18 expressions in spleen although no significant differences were recorded in chickens vaccinated via IM and orally with S. typhimurium and S. typhimurium.pcDNA3.1. Hence, single oral administrations of the attenuated S. typhimurium containing pcDNA3.1.H5 showed antibody, T cell and Th1-like cytokine responses against AIV in chickens. Whether the T cell response induced by vaccination is virus-specific and whether vaccination protects against AIV infection requires further study.

3,4-Methylenedioxymethamphetamine (Ecstasy) Decreases Inflammation and Airway Reactivity in a Murine Model of Asthma

Objective: 3,4-Methylenedioxymethamphetamine (MDMA), or ecstasy, is a synthetic drug used recreationally, mainly by young people. It has been suggested that MDMA has a Th cell skewing effect, in which Th1 cell activity is suppressed and Th2 cell activity is increased. Experimental allergic airway inflammation in ovalbumin (OVA)-sensitized rodents is a useful model to study Th2 response; therefore, based on the Th2 skewing effect of MDMA, we studied MDMA in a model of allergic lung inflammation in OVA-sensitized mice. Methods: We evaluated cell trafficking in the bronchoalveolar lavage fluid, blood and bone marrow; cytokine production; L-selectin expression and lung histology. We also investigated the effects of MDMA on tracheal reactivity in vitro and mast cell degranulation. Results: We found that MDMA given prior to OVA challenge in OVA-sensitized mice decreased leukocyte migration into the lung, as revealed by a lower cell count in the bronchoalveolar lavage fluid and lung histologic analysis. We also showed that MDMA decreased expression of both Th2-like cytokines (IL-4, IL-5 and IL-10) and adhesion molecules (L-selectin). Moreover, we showed that the hypothalamus-pituitary-adrenal axis is partially involved in the MDMA-induced reduction in leukocyte migration into the lung. Finally, we showed that MDMA decreased tracheal reactivity to methacholine as well as mast cell degranulation in situ. Conclusions: Thus, we report here that MDMA given prior to OVA challenge in OVA-sensitized allergic mice is able to decrease lung inflammation and airway reactivity and that hypothalamus-pituitary-adrenal axis activation is partially involved. Together, the data strongly suggest an involvement of a neuroimmune mechanism in the effects of MDMA on lung inflammatory response and cell recruitment to the lungs of allergic animals.