Increase In Number Of Lymphocytes Research Articles

Spiral ganglion neuron degeneration in aminoglycoside-deafened rats involves innate and adaptive immune responses not requiring complement.

Spiral ganglion neurons (SGNs) transmit auditory information from cochlear hair cells to the brain. SGNs are thus not only important for normal hearing, but also for effective functioning of cochlear implants, which stimulate SGNs when hair cells are missing. SGNs slowly degenerate following aminoglycoside-induced hair cell loss, a process thought to involve an immune response. However, the specific immune response pathways involved remain unknown. We used RNAseq to gain a deeper understanding immune-related and other transcriptomic changes that occur in the rat spiral ganglion after kanamycin-induced deafening. Among the immune and inflammatory genes that were selectively upregulated in deafened spiral ganglia, the complement cascade genes were prominent. We then assessed SGN survival, as well as immune cell numbers and activation, in the spiral ganglia of rats with a CRISPR-Cas9-mediated knockout of complement component 3 (C3). Similar to previous findings in our lab and other deafened rodent models, we observed an increase in macrophage number and increased expression of CD68, a marker of phagocytic activity and cell activation, in macrophages in the deafened ganglia. Moreover, we found an increase in MHCII expression on spiral ganglion macrophages and an increase in lymphocyte number in the deafened ganglia, suggestive of an adaptive immune response. However, C3 knockout did not affect SGN survival or increase in macrophage number/activation, implying that complement activation does not play a role in SGN death after deafening. Together, these data suggest that both innate and adaptive immune responses are activated in the deafened spiral ganglion, with the adaptive response directly contributing to cochlear neurodegeneration.

Oral Acute Toxicity, Influence on the Gastrointestinal Microbiota and in Vivo Anti-Salmonellosis Effect of Zizyphus Lotus (L.) and Ruta Chalepensis (L.) Essential Oils

Introduction: The aim of this study was to evaluate the chemical composition of Z. lotus (ZL) and R. chalepensis (RC) Essential Oils (EOs), the oral acute toxicity, influence on the gastrointestinal (GI) microbiota, and the in vivo anti-salmonellosis effect. Materials and Methods: The EOs were isolated using the steam distillation process, and bioactive components were identified by GC-MS analysis. Oral acute toxicity, influence on the GI flora composition, and the anti-salmonellosis effect were elucidated using in vivo methods on experimental animals. Results: The GC-MS allowed us to identify 33 and 58 components in Z. lotus and R. chalepensis, respectively. Di-isooctyl phthalate (89.857%) was found to be the major compound identified in ZL. The main compounds in RC were 2-undecanone (26.528 %) followed by 2-nonanone (13.404 %). The LD50 of EOs was found to be greater than 5000 mg/kg. Also, no negative influence to intestinal microbiota was detected. An important decrease in S. enterica ssp arizonae cells achieving a bactericidal effect was recorded in rats treated with the EOs of both plants at a dose of 400 mg/kg. In parallel, an important significant (p <0.05) increase in lymphocyte number was observed for all tested animals. A decrease in alkaline phosphatase (ALP), alanine aminotransferase(ALT), and aspartate aminotransferase (AST) levels were observed. Furthermore, a reduced blood sedimentation rate (ESR) was recorded in treated animals. Conclusions: The Z. lotus and R. chalepensis act effectively as anti-salmonellosis agents, which support the use of these plants to cure gastrointestinal infections.

126 Effect of astaxanthin supplementation on invitro embryo development and immune response of dairy cows

Astaxanthin is a carotenoid antioxidant reported to have beneficial effects on animals, including immune response and reproductive function. This study aimed to determine the effect of daily supplementation of dairy cows with astaxanthin on leukocyte population and oocyte developmental potential in summer. Lactating Holstein cows (n=45) from a compost barn in Paraná, Brazil, received 0 (control), 0.25 (low AST), or 0.5 (high AST) mg/kg per day of astaxanthin for 75 days in the summer (January to March 2020). Groups were homogeneous according to parity, days in milk, and milk yield. Blood cell count (white blood cells, lymphocyte, neutrophil, monocyte, basophil, and eosinophil) was performed on sodium citrate-treated blood samples collected every 14 days. Ovum pickup (OPU) was then conducted three times at a 20-day interval and oocytes underwent IVF to assess their developmental competence. Data were tested for normality of residues (Shapiro-Wilk test) and homogeneity of variances (F max test), and square root-transformed when premises for ANOVA were not met. One-way ANOVA (embryo development data; effect of astaxanthin) or two-way repeated-measures ANOVA (oocyte quality, and leukogram data; effect of astaxanthin, time, and interaction) followed by Tukey’s multiple comparisons test were performed using GraphPad Prism vs.7.0 (GraphPad Inc.). During the experimental period, animals were exposed to an average air temperature of 29.40±0.20°C and relative humidity of 58.00±0.80%. Physiological parameters were as follows: heart rate of 53.55±0.34 beats/min, respiratory rate of 48.39±0.31 breaths/min, body surface temperature of 32.83±0.11°C, and rectal temperature of 38.77±0.02°C. A higher white blood cell count was observed for the low AST group compared with control (P=0.0203) and high AST (P=0.0107) groups after 56 days of supplementation. For lymphocyte quantification, an effect of astaxanthin (P=0.0440) and astaxanthin×time of supplementation interaction (P=0.0239) were observed. The lower dose of astaxanthin caused an increase in lymphocyte number, which could be detected after 42 days of astaxanthin supplementation (P ≤ 0.05). No significant differences were detected for other leukocyte types. No effect of astaxanthin was observed on total number of oocytes recovered per cow except for the first OPU, in which more oocytes were retrieved from cows supplemented with 0.5 mg/kg per day of astaxanthin (9.92±1.95) compared with control (3.58±0.73; P=0.0179) and low AST (4.23±1.18; P=0.0358) groups. In addition, more viable oocytes (grades 1, 2, or 3 according to cytoplasm homogeneity and cumulus cells layers) were obtained from animals supplemented with 0.5 mg/kg per day of astaxanthin (3.17±0.39) compared with control (1.67±0.31; P=0.0050) and low AST (1.56±0.26; P=0.0022) groups. Interestingly, no differences were observed for invitro developmental potential among groups. These data suggest that a low dose of astaxanthin can affect lymphocyte mobilization, whereas a higher dose is required to improve the number of morphologically viable oocytes obtained by OPU from Holstein cows during summer.

Persistent lymphopenia in septic patients at Dr. Sardjito General Hospital, Yogyakarta

Sepsis triggers immune responseboth pro-inflammatory and anti-inflammatory. Lymphocytes play an important role in the regulation of the inflammatory response. The decrease in lymphocyte numbers due to continuous apoptosis by sepsiscan suppress the immune system and failure to resolve inflammation. Persistent lymphopenia is also associated with a poor prognosis of sepsis. Currently, there are limited studies about persistent lymphopenia in sepsis patients in low- and middle-income countries, including Indonesia. This study aimed to describe the sociodemographic, clinical, and laboratory patterns of sepsis patients with persistent lymphopenia. This was a descriptive study that analyzed patients’ medical records who were treated at the Department of Internal Medicine, Dr. Sardjito General Hospital, Yogyakarta from January 1st, 2016, to December 31th, 2017. Patients diagnosed with clinical sepsis and persistent lymphopenia were included in the study. The status of persistent lymphopenia was described as lymphocyte counts that remained low or lower (<1.62x103/L) on day 4± 24 h compared to the initial value at the time of sepsis diagnosis (day one). Information of patients’ individual and clinical characteristics, complete blood cell count profiles and culture results were included. The outcomes of interest were the survival status and length of stay of the patients. A total of 101 patients with sepsis and persistent lymphopenia were involved in this study. The average increase in lymphocyte numbers was 73.63 ± 426.86/µL. The main source of infection was pulmonary infection, with a mortality rate of 43.6% and a median survival of 19 days. The average length of stay was 13.1±6.8. Persistent lymphopenia in patients with sepsis has a high mortality. Further research is needed to determine the clinical ramifications of persistent lymphopenia.

Impact of Intrauterine Growth Restriction Diseases on The Umbilical Cord Blood CD34+ Cell Counts

Introduction: Different diseases in obstetrics and gynecology can affect the number of CD34+ cells in the umbilical cord blood. Objectives: This study aimed to evaluate the effect of Gestational Diabetes Mellitus (GDM), Gestational Hypertension (GHT) and Morbidly Adherent Placenta (MAP) on the content of CD34+ cells of umbilical cord blood and to compare the effectiveness of Sysmex XN20 analyzer to the flow cytometry method, which is the gold standard in CD34+ cells. Materials abd Methods: The umbilical cord blood (15 ml) was collected after the birth of the newborns. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Paque Plus. The cells were stained with Procount ™ Progenitor Cell Count Kit with PE Labeled monoclonal anti-CD34+ antibody then analyzed with Flow Cytometry or Sysmex XN20 without staining, to identify CD34+ cells named as hematopoietic progenitor cells (HPC), respectively. Results: Flow cytometric evaluation revealed a significantly elevated (p&lt;0.05) number of cord blood CD34+ cells in GDM and GHT groups compared with healthy controls. MAP patients had comparable CD34+ cells compared with healthy controls. A significant increase in lymphocyte counts was also observed in GDM and GHT groups compared with healthy controls. Sysmex analysis however only revealed an increase in lymphocyte numbers in GHT but picked no differences across groups in HPC. Correlation between Sysmex and flow cytometry results was weak in control, GHT, GDM and MAP groups r: 0570/p&lt;0.01, r: 0.5727/p: 0.0708, r:0.2149/p: 0.4779, r: 0.111/p: 0.779, respectively. Conclusions: CD34+ cells were significantly higher in the GHT and GDM groups compared with healthy control cord blood. The correlations between Flow cytometry and Sysmex were not strong.

GRANULOCYTE-COLONY STIMULATING FACTOR (G-CSF) AND GRANULOCYTE-MACROPHAGE CSF (GM-CSF) ADMINISTRATION ENRICHES FOR HIGHLY SUPPRESSIVE CD4+CD45RA-FOXP3HI CELLS IN LEUKAPHERESIS PRODUCTS OF RHESUS MONKEYS

Introduction: In humans, CD4+CD45RA-Foxp3hi T cells comprise a regulatory T cell (Treg) subset with highly suppressive function. We have previously shown that granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) administration enhances the incidence of peripheral blood CD4+CD25hiFoxp3hi Treg in non-human primates. Here, we examined whether GM-CSF/G-CSF administration enhances the incidence of CD4+CD45RA-Foxp3hi Treg in leukapheresis products (LP) of rhesus monkeys. Methods: Rhesus monkeys peripheral blood mononuclear cells (PBMC, n=3) were cultured with either GM-CSF (1ng/ml) or G-CSF (1ng/ml). Treg in PBMC were assessed based on their expression of CD45RA, CD25 and Foxp3. The percentages and phenotype of CD4+CD45RA-Foxp3hi Treg and CD4+CD45RA-Foxp3lo populations were evaluated. Naïve rhesus monkeys (n=6; 5-7kg) were treated sequentially with recombinant human GM-CSF (10 mg/kg/day for 4 days), then recombinant human G-CSF (10 mg/kg/day for 4 days), followed by leukapheresis. Similarly, Treg in PBMC, obtained before treatment, and in LP obtained after GM-CSF/GCSF administration were assessed. Additionally, LP CD4+CD45RA-CD25lo and CD4+CD45RA-CD25hi populations were flow-sorted (n=5) and assessed for their suppressive function. Results: In vitro, G-CSF did not enhanced Treg percentages. Meanwhile, GM-CSF enhanced the percentages of both CD4+CD25hiFoxp3hi and CD4+CD45RA-Foxp3hi Treg populations. In vivo, while G-CSF administration increased lymphocyte numbers, no increase in Treg percentages was observed. On the other hand, GM-CSF administration augmented the percentages of both CD4+CD25hiFoxp3hi and CD4+CD45RA-Foxp3hi Treg populations in peripheral blood. After combined G-CSF/GM-CSF administration, the incidences of CD4+CD45RA-Foxp3hi Treg increased significantly in LP (p<0.01), compared to peripheral blood before treatment. Furthermore, the ratio of CD4+CD45RA-Foxp3hi to CD4+CD45RA-Foxp3lo cells increased significantly (p<0.05). In LP, The CD4+CD45RA-CD25hi population expressed significantly higher levels of Foxp3, CTLA4 and Helios, compared to the CD4+CD45RA-CD25lo population (p<0.05). In 5 animals, LP flow-sorted CD4+CD45RA-CD25hi cells exhibited higher suppressive capacity of T cell proliferation in response to anti-CD2/CD3/CD28 stimulation, compared to the CD4+CD45RA-CD25hi population. Conclusions: G-CSF/GM-CSF administration enhances the incidences of highly suppressive CD4+CD45RA-Foxp3hi T cells in LP of mobilized rhesus monkeys. These observations further support the therapeutic potential of Treg-enriched LP from mobilized individuals. NIH grant U19 AI131453.

Hyperprogressive Disease in Patients With Urothelial Carcinoma or Renal Cell Carcinoma Treated With PD-1/PD-L1 Inhibitors.

A rapid progression pattern called hyperprogressive disease (HPD) has been observed during early cycles of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy. Data regarding HPD in patients with genitourinary cancer are limited. We included 203 patients with genitourinary cancer treated with PD-1/PD-L1 inhibitors between February 2015 and June 2018. HPD was defined as a greater than 50% increase in tumor burden, greater than 2-fold increase in tumor growth rate, or development of extensive (10 or more) new lesions. Patients (n= 102) with renal cell carcinoma (RCC) and patients (n= 101) with urothelial carcinoma (UC) were included. HPD was observed in 13 (6.4%) patients. The median overall survival for patients with progressive disease and HPD was 7.3 months and 3.5 months, respectively. HPD occurred more frequently in patients with UC than in those with RCC (11.9% vs. 0.9%; P= .01). Multivariate analysis showed that UC and creatinine above 1.2 mg/dL were independent predictive factors for HPD. A 30% increase in lymphocyte number following PD-1/PD-L1 inhibitor treatment was a negative predictor of HPD. The incidence of HPD in patients with UC treated with paclitaxel-based chemotherapy was one-third of those treated with PD-1/PD-L1 inhibitors. HPD developed predominantly in patients with UC, and the incidence of HPD in patients with RCC was negligible. Treatment with PD-1/PD-L1 inhibitors should be prescribed with caution in patients with UC and creatinine above 1.2 mg/dL.

Lack of IL-17 Receptor A signaling aggravates lymphoproliferation in C57BL/6 lpr mice

Defects in Fas function correlate with susceptibility to systemic autoimmune diseases like autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosus (SLE). C57BL/6 lpr (B6/lpr) mice are used as an animal model of ALPS and develop a mild SLE phenotype. Involvement of interleukin-17A (IL-17A) has been suggested in both phenotypes. Since IL-17 receptor A is part of the signaling pathway of many IL-17 family members we investigated the role of IL-17 receptor signaling in disease development in mice with a B6/lpr background. B6/lpr mice were crossed with IL-17 receptor A deficient (IL-17RA KO) mice and followed over time for disease development. IL-17RA KO/lpr mice presented with significantly enhanced lymphoproliferation compared with B6/lpr mice, which was characterized by dramatic lymphadenomegaly/splenomegaly and increased lymphocyte numbers, expansion of double-negative (DN) T-cells and enhanced plasma cell formation. However, the SLE phenotype was not enhanced, as anti-nuclear antibody (ANA) titers and induction of glomerulonephritis were not different. In contrast, levels of High Mobility Group Box 1 (HMGB1) and anti-HMGB1 autoantibodies were significantly increased in IL-17RA KO/lpr mice compared to B6/lpr mice. These data show that lack of IL-17RA signaling aggravates the lymphoproliferative phenotype in B6/lpr mice but does not affect the SLE phenotype.

Effects of a 1,2,4-triazole derivative liposome emulsion on the innate and adaptive immunity of puppies vaccinated against canine parvovirus and canine distemper

The aim of the study was the evaluate the immunomodulating effect of a 1,2,4-triazole derivative liposome emulsion (Trifuzol) in puppies vaccinated against parvovirus enteritis and canine distemper. The used Trifuzol liposome emulsion led to a significant increase in the absolute number of lympho-cytes and their immunoregulatory subpopulations, phagocytic activity of neutrophils. The level of antibodies against parvovirus enteritis (CPV) and canine distemper (CDV) in vaccinated and Trifuzol-treated puppies reached zero values which were statistically significantly lower than those in vac-cinated-only puppies (21.0 U/mL and 27.0 U/mL, respectively). It was concluded that the tested liposome emulsion of Trifuzol had an positive effect on the humoral immunity in puppies and can be used in clinical practice as an immunomodulatory agent.

Effectof Castration on Some Immunological Aspects in Male Albino Rat

The current study aimed to evaluate the effect of surgical and chemical castration on some immunological aspects in adult male albino rats. A total number of forty adult male albino rats weighing 220±20 g and averaging 4 months old were used. Rats were divided into four equal groups. Group 1, intact control group; group 2, sham castrated group; group3, surgically castrated group and group 4, chemically castrated group. Relative thymus and spleen weight, peripheral total and differential leukocytic count and relative expression of TNFα gene were recorded at 2 and 4 weeks after castration. The obtained results revealed that surgical and chemical castration resulted in a significant increase in relative thymus and spleen weight. Peripheral total leukocytic count was significantly increased in surgically and chemically castrated groups as compared to intact control and sham groups. Differential leukocytic count revealed a significant increase in lymphocyte number and a significant decrease in neutrophil number in surgically and chemically castrated groups as compared to intact control and sham groups. Real-time quantitative PCR analysis of TNFα gene expression in spleen revealed that surgical and chemical castration resulted in significant up regulation of TNFα gene expression. So, it concluded that surgical and chemical castration improved immunity and testosterone has an immunosuppressive effect in adult male albino rats.

Arneth Count In Different Phases of Menstrual Cycle in the Age Group 18- 22 Yrs

Background & Objectives: Blood leukocyte count and differential count varies from individual to individual and diurnal changes are noted in various studies. In present study we are investigating the effect of cyclic changes in gonadotropic hormones during normal menstrual cycle on the differential leukocyte count and in particular the nuclear lobe variation in the different phases of menstrual cycle in young women of 18-22 years old with normal past menstrual cycles. Methodology: First year undergraduate students of Pushpagiri Medical College in the age group of 18-22 years were included in the study. 44 healthy female students with regular menstrual cycle of 28±2days duration participated in the study, students with irregular cycles, gynaecological disorders; history of drug intake and acute illness were excluded from the study. The blood was collected under aseptic precautions and peripheral blood smears were formed. The smears were stained with Leishman’s stain following standard protocol and labelled them. The differential leukocyte count and arneth count were observed in the stained smear and recorded. To study variation the blood samples were collected on 5th day of the cycle (menstrual), 14 th day of the cycle (proliferative) and 21 st day of the cycle (luteal). The results were analysed using one way ANOVA between 3 groups and posthoc analysis if applicable. Results & Conclusion: Different phases of menstrual cycle showed an statistically significant difference in Differential count of Neutrophils & Lymphocytes but other cells Eosinophil count, Monocyte & Basophil count had no significant difference which suggested that gonadotropic hormones had influence on leukocytes both granulocyte (Neutrophil) & agranulocyte (Lymphocyte) where we noticed increased Neutrophil count during luteal phase and least increase in number of Lymphocytes during luteal phase. In arneth count we had statistically significant difference in 2, 3, 4 and 5 lobed nuclei of Neutrophils and specifically 2 and 3 lobed Neutrophil count increased in luteal phase suggesting new (young) neutrophils released in the circulation

Atg5 Is Essential for the Development and Survival of Innate Lymphocytes.

Autophagy is an essential cellular survival mechanism that is required for adaptive lymphocyte development; however, its role in innate lymphoid cell (ILC) development remains unknown. Furthermore, the conditions that promote lymphocyte autophagy during homeostasis are poorly understood. Here, we demonstrate that Atg5, an essential component of the autophagy machinery, is required for the development of mature natural killer (NK) cells and group 1, 2, and 3 innate ILCs. Although inducible ablation of Atg5 was dispensable for the homeostasis of lymphocyte precursors and mature lymphocytes in lymphoreplete mice, we found that autophagy is induced in both adaptive and innate lymphocytes during homeostatic proliferation in lymphopenic hosts to promote their survival by limiting cell-intrinsic apoptosis. Induction of autophagy through metformin treatment following homeostatic proliferation increased lymphocyte numbers through an Atg5-dependent mechanism. These findings highlight the essential role for autophagy in ILC development and lymphocyte survival during lymphopenia.

Repeated high-dose (5 × 108 TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits

ABSTRACTConcern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×108 TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×108 TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×108 TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only.

In Vivo Safety of Aqueous Extracts of Maytemus putterlickoides, Senna spectabilis and Olinia usambarensis on Mice Models

Plant products are used as the primary health care in developing countries due to their availability and affordability compared to conventional methods. It is estimated that more than 80% of the world’s population use herbal preparations in the management and treatment of diseases. Herbal products are now readily available in supermarkets and drug stores. The therapeutic value of these herbal products is believed to be due to the presence of bioactive elements present in the plant parts. Toxicity studies should, however be carried to ascertain the safety of the herbal preparation. In this study, safety studies were carried out through biochemical assays, histopathology and hematological tests. The plant extracts led to changes in body weight, hematological and histopathological changes like increase in lymphocyte number. High dose of orally administered Olinia usambarensis also caused microcytic hypochromic anemia. Senna spectabilis and Olinia usambarensis revealed intense infiltration of inflammatory cells causing necrosis and loss of cellular details of the kidney. This study will enhance understanding of the safety of ethno-medical materials in the management of diarrhea caused by bacterial pathogens.

Abstract 480: Maintenance immunotherapy following carboplatin (CBDCA) - pemetrexed (PEM) chemotherapy in advanced adenocarcinoma (ADK) of the lung: A phase II study.

Abstract Background: Continuation maintenance therapy with PEM vs. placebo has been shown to improve progression-free survival (PFS) and overall survival (OS), in patients with advanced non squamous non small cell lung cancer, at the price of a substantial toxicity. Nevertheless, in these patients the observed lymphocytopenia induced by chemotherapy, is a negative independent prognostic factor. Bacterial extracts (OM-85) have been shown to enhance the activation of both IgM memory B lymphocytes (CD24+/CD27+ cells) and inteleukin-2 receptor-expressing lymphocytes (CD25+ cells) (Int J Immunopathol Pharmacol. 2006;19:551). In addition, we have demonstrated that 13-cis retinoic acid (RA) restored the chemotherapy-depressed immune function (Clin Cancer Res 2001;7:1251). With this rationale, we designed a phase II study of maintenance immunotherapy after first line CBDCA-PEM chemotherapy in order to maintain an achieved response, or at least stable disease, for as long as possible, with acceptable side effects. Methods: Histologically/cytologically confirmed patients with stage IIIB or IV non operable ADK of the lung with measurable disease, ECOG PS 0-2, age 18-75 years and adequate bone marrow, renal and liver function were eligible for the study. Treatment consisted of 6 courses of PEM 500 mg/m2 and CBDCA, AUC=5, on day 1 every 3 weeks. Patients with a clinical benefit were treated with OM-85, 7 mg/day, 10 days/month and RA 0.5 mg/kg, 5 days/week, 3 weeks/month, both given until progression. Results: From September 2007 to March 2012, 54 patients, with a median age of 65 years (range 33-75), 50% stage IIIB and 50% stage IV, were entered into the study. At a median follow up of 22 months, clinical benefit was observed in 41 patients (75%); Complete response 8 (14%), partial response 21 (39%), stable disease 12 (22%), progressive disease 13 (25%). One-year OS rate was 69%. After immunotherapy, a statistically significant (P&amp;lt;0.001) increase in lymphocyte number was observed in responders. Median PFS was 10.2 months, while median OS was 27.6 months. Four patients, rendered operable with treatment, underwent a radical surgical procedure. Grade 4 renal toxicity was observed in 1 patient, while grade 3-4 hematologic toxicity occurred in 9 patients (17%). Conclusion: This study shows that maintenance immunotherapy with the combination of OM-85 and RA, administered after chemotherapy in advanced ADK of the lung, is feasible and induces a statistically significant raise in lymphocyte number. In addition a favorable impact on PFS and OS was observed. Future randomized studies to investigate the role of maintenance immunotherapy strategies, are in program Citation Format: Francesco Recchia, Giampiero Candeloro, Alisia Cesta, Anna Di Blasio, Cornelia O.C. Recchia, Stefano Necozione, Giovambattista Desideri, Silvio Rea. Maintenance immunotherapy following carboplatin (CBDCA) - pemetrexed (PEM) chemotherapy in advanced adenocarcinoma (ADK) of the lung: A phase II study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 480. doi:10.1158/1538-7445.AM2013-480

Influence of Stimforte on the immunologic characteristics of mice against induced immunosuppression

Event Abstract Back to Event Influence of Stimforte on the immunologic characteristics of mice against induced immunosuppression Olga V. Lebedinskaya1*, Elena A. Lebedinskaya1, Evgenia V. Fadeeva1, Nelly K. Akhmatova2, Dmitriy G. Maldov2 and Mikhail V. Kiselevsky2 1 Acad. E.A. Wagner Perm State Medical Academy, Russia 2 N.N. Blokhin Russian Cancer Research Center RAMS, Russia The aim of study was the analysis of Stimforte effect on immunological parameters in mice against induced immunosuppression. Investigation was carried out with 80 BALB/c mice there were injected either with cyclophosphane (CP) and Stimforte in different combinations or with physiological solution (control group). The immunophenotype of mononuclear leukocytes (ML) isolated from animal spleen and killer activity against YAK-1 tumor line were defined. Morphological investigations of Romanosvky-Giemsa-stained smears were administrated. CP administered (100 mg/kg) within 3 days evoked immunosuppression that was manifested in nearly 7-fold lowering of ML number in mice spleen as compared with control group. ML population in CP-received animal group was represented by mature lymphocytes, whereas control group demonstrated considerable amount of young lymphoid cells in spleen. Animals against CP introduction exhibited significant decrease in natural killer (NK) and pronounced reduction in their NK-activity. Stimforte injection against CP-induced immunosuppression increased more than by 2-fold the ML content in mice spleen, when immature forms such as pro-lymphocytes were detected. In addition, Stimforte favored the normalization of NK content in spleen ML and their NK activity increment nearly to the initial values. Peripheral blood of animals under study also demonstrated the increase in granulocyte number. Thus, CP resulted in marked immunosuppression manifesting in lowering in total lymphocyte amount in mice peripheral blood and spleen, as well as declining in NK content in lymphocyte population as compared with intact animals. Stimforte administration against cytostatic-induced immunosuppression resulted in significant increase in lymphocyte number and normalization of their immunophenotype and function characteristics. Keywords: Stimforte, induced immunosuppression, cyclophosphane, immunophenotype, mononuclear leukocytes Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Lebedinskaya OV, Lebedinskaya EA, Fadeeva EV, Akhmatova NK, Maldov DG and Kiselevsky MV (2013). Influence of Stimforte on the immunologic characteristics of mice against induced immunosuppression. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00845 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Ms. Olga V Lebedinskaya, Acad. E.A. Wagner Perm State Medical Academy, Perm, Russia, lebedinska@mail.ru Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Olga V Lebedinskaya Elena A Lebedinskaya Evgenia V Fadeeva Nelly K Akhmatova Dmitriy G Maldov Mikhail V Kiselevsky Google Olga V Lebedinskaya Elena A Lebedinskaya Evgenia V Fadeeva Nelly K Akhmatova Dmitriy G Maldov Mikhail V Kiselevsky Google Scholar Olga V Lebedinskaya Elena A Lebedinskaya Evgenia V Fadeeva Nelly K Akhmatova Dmitriy G Maldov Mikhail V Kiselevsky PubMed Olga V Lebedinskaya Elena A Lebedinskaya Evgenia V Fadeeva Nelly K Akhmatova Dmitriy G Maldov Mikhail V Kiselevsky Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Strain-Dependent Airway Hyperresponsiveness and a Chromosome 7 Locus of Elevated Lymphocyte Numbers in Cystic Fibrosis Transmembrane Conductance Regulator-Deficient Mice

We previously observed the lungs of naive BALB/cJ Cftr(tm1UNC) mice to have greater numbers of lymphocytes, by immunohistochemical staining, than did BALB wild type littermates or C57BL/6J Cftr(tm1UNC) mice. In the present study, we initially investigated whether this mutation in Cftr alters the adaptive immunity phenotype by measuring the lymphocyte populations in the lungs and spleens by FACS and by evaluating CD3-stimulated cytokine secretion, proliferation, and apoptosis responses. Next, we assessed a potential influence of this lymphocyte phenotype on lung function through airway resistance measures. Finally, we mapped the phenotype of pulmonary lymphocyte counts in BALB × C57BL/6J F2 Cftr(tm1UNC) mice and reviewed positional candidate genes. By FACS analysis, both the lungs and spleens of BALB Cftr(tm1UNC) mice had more CD3(+) (both CD4(+) and CD8(+)) cells than did littermates or C57BL/6J Cftr(tm1UNC) mice. Cftr(tm1UNC) and littermate mice of either strain did not differ in anti-CD3-stimulated apoptosis or proliferation levels. Lymphocytes from BALB Cftr(tm1UNC) mice produced more IL-4 and IL-5 and reduced levels of IFN-γ than did littermates, whereas lymphocytes from C57BL/6J Cftr(tm1UNC) mice demonstrated increased Il-17 secretion. BALB Cftr(tm1UNC) mice presented an enhanced airway hyperresponsiveness to methacholine challenge compared with littermates and C57BL/6J Cftr(tm1UNC) mice. A chromosome 7 locus was identified to be linked to lymphocyte numbers, and genetic evaluation of the interval suggests Itgal and Il4ra as candidate genes for this trait. We conclude that the pulmonary phenotype of BALB Cftr(tm1UNC) mice includes airway hyperresponsiveness and increased lymphocyte numbers, with the latter trait being influenced by a chromosome 7 locus.

The Effect ofTaraxacum officinaleHydroalcoholic Extract on Blood Cells in Mice

Objectives. Dandelion (Taraxacum officinale) is a herbaceous perennial plant of the family Asteraceae and has medicinal and culinary uses. Dandelion has been used as a remedy for anemia, purifing the blood, and providing immune modulation. Therefore, the aim of this study was to investigate the effect of hydro alcoholic extract on blood cells in mice. Methods. Five groups each including ten adult female (Balb/C) mice weighing 30 ± 5 g were chosen. Normal saline was administered as placebo for group, and dandelion hydro alcoholic extract in doses of 50,100, and 200 mg/kg was injected intraperitoneally for 20 days to test groups and the last group was control group.WBC, RBC, HB, HCT, platelet, and other cells were measured with automated cell counter. Main Results. The number of RBC and the rate of HB in three doses of 100 and 200 mg/kg significantly increased (P < 0.05). As compared with control group, the number of WBC in three doses of 50, 100, and 200 mg/kg increased, but it was significantly in 200 mg/kg dandelion treated group as compared with control group(P < 0.05). The rate of platelet in three doses of 50, 100 and 200 mg/kg significantly decreased as compared with control group (P < 0.01). 3 doses of dandelion increased lymphocyte numbers significantly compared with controls. Conclusion. The study indicates efficacy of dandelion extract on RBC and HB in doses of 50, 100, and 200 mg/kg and in 200 mg/kg on WBC to achieve normal body balance.

Leucocyte profiles and corticosterone in chicks of southern rockhopper penguins

The immune system is essential for health and survival of vertebrates, yet still little is known about the ontogeny of the immune system in wild birds. The southern rockhopper penguin (Eudyptes chrysocome chrysocome) is a semi-altricial seabird with a long developmental period and reversed hatching asynchrony, favouring the survival of B-chicks. We compared leucocyte counts and baseline corticosterone levels of southern rockhopper penguin chicks under different preconditions such as sex and origin from an A- or B-egg from 4 to 51days of age. We conducted an experiment to compare leucocyte profiles and baseline corticosterone levels in A- and B-chicks in single-egg clutches as well as in B-chicks from normal two egg-clutches (one A- and one B-egg). None of these treatments influenced leucocyte counts or corticosterone levels, indicating a similar investment in the immune system. Our main finding was an increase of leucocytes/10,000 erythrocytes with age, which was mainly caused by an increase in lymphocyte numbers. This suggests differential investment into acquired immunity at this stage of development. As the granulocyte/lymphocyte (G/L) ratio did not change with age or body condition, G/L ratios seem not to reflect stress caused by poor provisioning of penguin chicks. This was also reinforced by the decrease of plasma corticosterone levels with age. Body condition was negatively correlated with monocyte numbers, suggesting a poorer health status of penguin chicks in poorer body condition. Yet, there was no link between body condition and other leucocyte parameters, indicating that chicks in a good body condition did not additionally invest into their immune system.

Health status and nesting pattern in male gray mouse lemurs (Microcebus murinus)

Summary.— In the Gray Mouse Lemur, a nocturnal Malagasy primate, nest sharing during the diurnal sleeping period provides significant thermoregulatory advantages. Using socially housed captive male mouse lemurs, we tested the hypothesis that males would present differential physiological parameters depending on their nest sharing patterns at the beginning of the breeding season. Nest composition, and health status inferred from body weight, reproductive activity (testis width) and level of immune activity (lymphocyte number) were recorded at the beginning of the breeding season and after 4 weeks in newly formed 4 groups of 5 adult males. One nest was occupied by 3 males or more in 85 % of the surveys, and 14 cases of males found alone in a nest were recorded, distributed over 65 % of the surveys. Males found alone or in pairs lost significantly more weight after the 4 weeks of social grouping than males found in groups of 3 or more individuals in a nest. Additionally, males expelled from common nests had reduced immune activity prior to social grouping than nest associated males. Nest associated males had little change in their lymphocyte numbers after the 4 weeks of social grouping, whereas isolated males exhibited a pronounced increase in lymphocyte numbers. These results indicate that, in mouse lemurs, nest-sharing pattern at the beginning of the breeding season is a complex process, yielding diverse energetic and immunological consequences.