Humoral Mediated Immune Responses Research Articles

Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs.

The central nervous system (CNS) influences the immune system generally by regulating the systemic concentration of humoral substances (e.g., cortisol and epinephrine), whereas the peripheral nervous system (PNS) communicates specifically with the immune system according to local interactions/connections. An imbalance between the components of the PNS might contribute to pathogenesis and the further development of certain diseases. In this review, we have explored the "thread" (hardwiring) of the connections between the immune system (e.g., primary/secondary/tertiary lymphoid tissues/organs) and PNS (e.g., sensory, sympathetic, parasympathetic, and enteric nervous systems (ENS)) in health and disease in vitro and in vivo. Neuroimmune cell units provide an anatomical and physiological basis for bidirectional crosstalk between the PNS and the immune system in peripheral tissues, including lymphoid tissues and organs. These neuroimmune interactions/modulation studies might greatly contribute to a better understanding of the mechanisms through which the PNS possibly affects cellular and humoral-mediated immune responses or vice versa in health and diseases. Physical, chemical, pharmacological, and other manipulations of these neuroimmune interactions should bring about the development of practical therapeutic applications for certain neurological, neuroimmunological, infectious, inflammatory, and immunological disorders/diseases.

Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer.

Small synthetic TLR7/8-agonists can be used as vaccine adjuvants to enhance cell and humoral-mediated immune responses to specific antigens. Despite their potency, after local injection they can be dispersed to undesired body parts causing high reactogenicity, limiting their clinical applications. Here we describe a vaccination strategy that employs the covalent conjugate of a mannose and TLR7/8 agonist as a vaccine adjuvant to take advantage of mannose binding C-type lectins on dendritic cells to enhance the vaccine's immunogenicity. The mannose-TLR7/8 agonist conjugate can self-assemble into nanoparticles with the hydrophilic mannose on the outside and hydrophobic TLR7/8 agonist inside. Although its ability to stimulate HEK-BlueTM hTLR7/8 cells dropped, it can efficiently stimulate mouse bone marrow-derived dendritic cells as indicated by the up-regulation of CD80 and CD86, and higher cytokine expression levels of TNF-α, IL6, and IL-12p70 than the native TLR7/8 agonist. In vivo, vaccination using the SARS-CoV-2 RBD trimer as the antigen and the conjugate as the adjuvant induced a significantly higher amount of IgG2a. These results suggest that the mannose-TLR7/8-agonist conjugate can be used as an effective vaccine adjuvant.

Sarcoidosis and autoimmunity: In the depth of a complex relationship.

Sarcoidosis is a chronic granulomatous disease that can virtually affect any organ. Its etiology is unknown, although it has been proposed that environmental or biological agents can act as triggers, ultimately leading to chronic inflammation in genetically predisposed individuals. The main component of sarcoid inflammation is represented by an exaggerated T- lymphocytic cellular response to a putative antigen that could not be efficiently cleared in the patient. However, several clinical and immunological observations, such as the association of sarcoidosis to autoimmune diseases or the presence of autoantibodies in the serum of patients with sarcoidosis, suggest that humoral-mediated immune response might also play a role in the pathogenesis of sarcoidosis. The aim of this review is to deepen the relationship between sarcoidosis and autoimmunity, by analyzing the most recent advances and proposing new fields of research.

Distribution of nerve fibers and nerve-immune cell association in mouse spleen revealed by immunofluorescent staining

The central nervous system regulates the immune system through the secretion of hormones from the pituitary gland and other endocrine organs, while the peripheral nervous system (PNS) communicates with the immune system through local nerve-immune cell interactions, including sympathetic/parasympathetic (efferent) and sensory (afferent) innervation to lymphoid tissue/organs. However, the precise mechanisms of this bi-directional crosstalk of the PNS and immune system remain mysterious. To study this kind of bi-directional crosstalk, we performed immunofluorescent staining of neurofilament and confocal microscopy to reveal the distribution of nerve fibers and nerve-immune cell associations inside mouse spleen. Our study demonstrates (i) extensive nerve fibers in all splenic compartments including the splenic nodules, periarteriolar lymphoid sheath, marginal zones, trabeculae, and red pulp; (ii) close associations of nerve fibers with blood vessels (including central arteries, marginal sinuses, penicillar arterioles, and splenic sinuses); (iii) close associations of nerve fibers with various subsets of dendritic cells, macrophages (Mac1+ and F4/80+), and lymphocytes (B cells, T helper cells, and cytotoxic T cells). Our data concerning the extensive splenic innervation and nerve-immune cell communication will enrich our knowledge of the mechanisms through which the PNS affects the cellular- and humoral-mediated immune responses in healthy and infectious/non-infectious states.

Immunofluorescence characterization of innervation and nerve-immune cell interactions in mouse lymph nodes.

The peripheral nervous system communicates specifically with the immune system via local interactions. These interactions include the “hardwiring” of sympathetic/ parasympathetic (efferent) and sensory nerves (afferent) to primary (e.g., thymus and bone marrow) and secondary (e.g., lymph node, spleen, and gut-associated lymphoid tissue) lymphoid tissue/organs. To gain a better understanding of this bidirectional interaction/crosstalk between the two systems, we have investigated the distribution of nerve fibres and PNS-immune cell associations in situ in the mouse lymph node by using immunofluorescent staining and confocal microscopy/ three-dimensional reconstruction. Our results demonstrate: i) the presence of extensive nerve fibres in all compartments (including B cell follicles) in the mouse lymph node; ii) close contacts/ associations of nerve fibres with blood vessels (including high endothelial venules) and lymphatic vessels/sinuses; iii) close contacts/associations of nerve fibres with various subsets of dendritic cells (e.g., B220+CD11c+, CD4+CD11c+, CD8a+ CD11c+, and Mac1+CD11c+), Mac1+ macrophages, and B/T lymphocytes. Our novel findings concerning the innervation and nerve-immune cell interactions inside the mouse lymph node should greatly facilitate our understanding of the effects that the peripheral nervous system has on cellular- and humoral-mediated immune responses or vice versa in health and disease.

British Society for Gene and Cell Therapy Annual Conference Wednesday 19th June – Friday 21st June 2019 University of Sheffield, Sheffield, UK www.bsgct.org

British Society for Gene and Cell Therapy Annual Conference Wednesday 19th June – Friday 21st June 2019 University of Sheffield, Sheffield, UK www.bsgct.org

Distribution of non-myelinating Schwann cells and their associations with leukocytes in mouse spleen revealed by immunofluorescence staining.

The nervous system and the immune system communicate extensively with each other in order to maintain homeostasis and to regulate the immune response. The peripheral nervous system (PNS) communicates specifically with the immune system according to local interactions, including the “hardwiring” of sympathetic/parasympathetic (efferent) and sensory nerves (afferent) to lymphoid tissue and organs. To reveal this type of bidirectional neuroimmune interaction at the microscopic level, we used immunofluorescent staining of glial fibrillary acidic protein (GFAP) coupled with confocal microscopy/3D reconstruction to reveal the distribution of nonmyelinating Schwann cells (NMSCs) and their interactions with immune cells inside mouse spleen. Our results demonstrate i) the presence of an extensive network of NMSC processes in all splenic compartments including the splenic nodules, periarteriolar lymphoid sheath (PALS), marginal zone, trabecula, and red pulp; ii) the close association of NMSC processes with blood vessels (including central arteries and their branches, marginal sinuses, penicillar arterioles and splenic sinuses); iii) the close “synapse-like” interaction/association of NMSC processes with various subsets of dendritic cells (DCs; e.g., CD4+CD11c+ DCs, B220+CD11c+ DCs, and F4/80+ CD11c+ DCs), macrophages (F4/80+), and lymphocytes (B cells, CD4+ T helper cells). Our novel findings concerning the distribution of NMSCs and NMSC-leukocytes interactions inside mouse spleen should improve our understanding of the mechanisms through which the PNS affects cellular- and humoral-mediated immune responses in a variety of health conditions and infectious/non-infectious diseases.

Transcriptomic analysis of Ehrlichia ruminantium during the developmental stages in bovine and tick cell culture

The use of bioinformatics tools to search for possible vaccine candidates has been successful in recent years. In an attempt to search for additional vaccine candidates or improve the current heartwater vaccine design, a genome-wide transcriptional profile of E. ruminantium (Welgevonden strain) replicating in bovine endothelial cells (BA886) and Ixodes scapularis embryonic tick cells (IDE8) was performed. The RNA was collected from the infective extracellular form, the elementary bodies (EBs) and vegetative intracellular form, reticulate bodies (RBs) and was used for transcriptome sequencing. Several genes previously implicated with adhesion, attachment and pathogenicity were exclusively up-regulated in the EBs from bovine and tick cells. Similarly, genes involved in adaptation or survival of E. ruminantium in the host cells were up‐regulated in the RBs from bovine cells. Thus, it was concluded that those genes expressed in the EBs might be important for infection of mammalian and tick host cells and these may be targets for both cell and humoral mediated immune responses. Alternatively, those exclusively expressed in the RBs may be important for survival in the host cells. Exported or secreted proteins exclusively expressed at this stage are ideal targets for the stimulation of cytotoxic T-lymphocyte (CTL) immune responses in the host.

Immunofluorescent characterization of non-myelinating Schwann cells and their interactions with immune cells in mouse mesenteric lymph node.

The central nervous system (CNS) influences the immune system in a general fashion by regulating the systemic concentration of humoral substances, whereas the autonomic nervous system communicates specifically with the immune system according to local interactions. Data concerning the mechanisms of this bidirectional crosstalk of the peripheral nervous system (PNS) and immune system remain limited. To gain a better understanding of local interactions of the PNS and immune system, we have used immunofluorescent staining of glial fibrillary acidic protein (GFAP), coupled with confocal microscopy, to investigate the non-myelinating Schwann cell (NMSC)-immune cell interactions in mouse mesenteric lymph nodes. Our results demonstrate: i) the presence of extensive NMSC processes and even of cell bodies in each compartment of the mouse mesenteric lymph node; ii) close associations/interactions of NMSC processes with blood vessels (including high endothelial venules) and the lymphatic vessel/sinus; iii) close contacts/associations of NMSC processes with various subsets of dendritic cells (such as CD4+CD11c+, CD8+CD11c+ dendritic cells), macrophages (F4/80+ and CD11b+ macrophages), and lymphocytes. Our novel findings concerning the distribution of NMSCs and NMSC-immune cell interactions inside the mouse lymph node should help to elucidate the mechanisms through which the PNS affects cellular- and humoral-mediated immune responses or vice versa in health and disease.

Abstract 642: Detection of circulating antibodies against KRAS in patients with advanced cancers

Abstract Introduction: KRAS gene plays a major role in tumorigenesis, cell proliferation and survival. Yet, there has been no effective targeted therapy against KRAS mutation-mediated tumors. We hypothesized that KRAS can induce humoral-mediated immune response. Methods: Plasma or serum samples from patients with progressing advanced cancers with or without KRAS mutations were tested for the presence of circulating KRAS antibodies. We used the Maverick Detection System (Genalyte, San Diego, CA), which can perform real-time detection of macromolecules in crude samples using biologically functionalized silicon photonic biosensors lithographically printed on disposable silicon chips. Results: We collected serum or plasma samples from 213 patients with advanced cancers (KRAS-mutant, N=100; KRAS wild-type, N=113) and 50 (23%) were found to have circulating KRAS antibodies. There was no association between KRAS antibodies and tumor KRAS mutation status (21/100, 21% for KRAS-mutant vs. 29/113, 26% for KRAS wild-type; P=0.52). In addition, there was no difference in detection of KRAS antibodies in colorectal cancer (21/89, 24%) compared to other cancers (29/124, 23%; P=1.00). There was no difference in the median survival in patients with KRAS antibodies compared to patients without KRAS antibodies (9.0 months vs. 10.1 months; P= 0.825). Similarly, there was no difference in the median survival according to the presence of circulating KRAS antibodies in subgroups of patients with tumor KRAS mutations (P= 0.96) and without tumor KRAS mutations (P=0.63). On the contrary, the median survival of patients with tumor KRAS mutation was shorter compared to patients with KRAS wild-type (7.2 months vs. 11.5 months; P<0.001). Conclusion: Circulating KRAS antibodies can be detected in 23% of patients with advanced cancers. Biological implications of circulating KRAS antibodies remain to be understood. Citation Format: Ed Kheder, Helen J. Huang, Alice Wu, David S. Hong, Sarina A. Piha-Paul, Daniel D. Karp, Siqing Fu, Vivek Subbiah, Apostolia M. Tsimberidou, Aung Naing, Adi Diab, Milind Javle, Scott Kopetz, Anil K. Sood, Jonathan M. Kurie, Funda Meric-Bernstam, Martin Gleeson, Filip Janku. Detection of circulating antibodies against KRAS in patients with advanced cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 642. doi:10.1158/1538-7445.AM2017-642

In vivo effect of Commiphora swynnertonii ethanolic extracts on Trypanosoma congolense and selected immunological components in mice

BackgroundThe search for alternative trypanocidal compounds which can be available at affordable price is of paramount importance for control of trypanosomosis in human and animals. The current study evaluates the in vivo activity of ethanolic stem bark extracts on Trypanosoma congolense and selected immunological components in an inbred Swiss albino mouse model.MethodsGroups of mice infected with T. congolense were treated with the stem bark extracts at a rate of 1000 mg/kg, 1500 mg/kg, and 2000 mg/kg, twice a day in one set and thrice a day in another setting for three days consecutively. Negative (infected and untreated) and positive (infected treated with diminazene diaceturate at 3.5 mg/kg) control groups were used. Levels of parasitaemia were monitored daily for the first 10 days and thereafter 2–3 times per week to the end of experiment. In the other setting, uninfected mice, randomized in groups were treated with the extract but categorized as: thorough mixed extract (TME) and supernatant extract (SE) each at 500 mg/kg and 1500 mg/kg, in 8 hourly intervals respectively for three days consecutively. Control group was administered with phosphate buffered saline with glucose at 0.1 ml/10 g in a similar manner as for the extract. Whole blood and spleen were taken 24 h after the last treatment for hematological and histopathological analysis.ResultsThe groups that received the extracts at 8 hourly intervals drastically reduced the parasitaemia. The higher dose of SE significantly reduced the percentage of lymphocytes (P < 0.05). Both high and low dose of TME significantly reduced lymphocytes percent (P < 0.05) while percent of neutrophils and monocytes increased significantly (P < 0.05). Histopathological changes of the spleen in the mice treated with higher concentrations of the extract of C. swynnertonii were suggestive of lymphocytes toxicity.ConclusionThe current study has provided evidence that, in vivo trypanocidal activity of ethanolic bark extracts of C. swynnertonii is probably affected by its negative effect on humoral mediated immune response. Further studies are recommended to determine its potential as an alternative source of lead compounds for trypanocidal drug discovery.

Additive toxic effect of deltamethrin and cadmium on hepatic, hematological, and immunological parameters in mice

Exposure to natural and man-made environmental toxins concurrently can pose a greater threat to multiple organs. In the present work, we investigated interactions between deltamethrin (DM) and cadmium (Cd), whose mechanisms of action in humans are poorly understood. Albino mice were randomly divided into four groups, each containing six mice: saline as control, DM-treated, cadmium chloride (CdCl2)-treated, and CdCl2 plus DM treated. After 2 weeks of treatment biochemical and hematological effects, total leukocyte count (TLC), differential leukocyte count, humoral-mediated immune responses, and histopathological studies were conducted. Mice exposed to DM and Cd showed a significant increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Also, DM and Cd administration resulted in suppression of humoral immunity, erythrocyte count, hemoglobin, hematocrit, and TLC. Histopathological evidence revealed hepatic damage, supporting the AST and ALT findings. Cd and DM exhibited an additive type of toxicity. It could be concluded that these toxins either target different cellular pathways, or the individual amounts used in this study were not enough to saturate the toxicological target, thus producing additive effects.

Delays do not cause oscillations in a corrected model of humoral mediated immune response

In the paper we focus on modelling immune system–cancer cells interactions with time delays included into the model. The first model we consider, is the (Feyissa and Banerjee, 2013) model of humoral immune response, for which we show that the non-negativity property is not preserved. This is the reason we propose a modification, which under the assumption that the tumour is non-immunogenic can be simplified into the system of three equations without delays, that is the second model we consider. For the simplified model we have made mathematical analysis, including asymptotic stability, as well as numerical analysis, showing wide spectrum of possible model dynamics, including globally stable steady state, bistability and oscillatory behaviour. The dynamics of the simplified model is numerically compared with the dynamics of the full model with time delays for the parameter values from the literature. It occurs that if tumour immunogenicity is low time delays have no significant influence on the full system and both systems behave similarly.

Evaluation of Antioxidant, Immunomodulatory Activities, and Safety of Ethanol Extract and Fractions of Gongronema latifolium Fruit.

Gongronema latifolium fruit has wide application in ethnomedicine, especially in maintaining healthy living and general body healing. We therefore investigated the antioxidant, immunomodulatory activities, and safety of its ethanol extract and fractions. The in vitro antioxidant activities of the extract and fractions were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) test while in vivo activities were determined using carbon tetrachloride (CCL4) induced oxidative stress. Cell and humoral mediated immune responses were also evaluated together with toxicity studies. The extract, ethyl acetate, and methanol fractions showed inhibition of DPPH radical with IC50s 120, 90, and 60 μg/mL, respectively. Methanol fraction at 200 mg/kg produced significant (P < 0.05) inhibition of lipid peroxidation (MDA conc. 1.2 μmol/L) compared to control (2.8 μmol/L). Both ethyl acetate and methanol fractions at 200 mg/kg produced significant (P < 0.05) phagocytic index of 0.021 and 0.025, respectively, compared with control (0.01). Significant (P < 0.05) elevations of white blood cells, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were noticed on the 91st day at higher doses. Generally, this study justified the traditional use of G. latifolium fruit for general body healing and maintenance of healthy living. Long term administration is safe on the haematological and biochemical systems especially at lower doses and its toxicity at higher doses is reversible.

One minute ultraviolet exposure inhibits Toxoplasma gondii tachyzoite replication and cyst conversion without diminishing host humoral-mediated immune response

We developed a protocol to inactivate Toxoplasma gondii (T. gondii) tachyzoites employing 1min of ultraviolet (UV) exposure. We show that this treatment completely inhibited parasite replication and cyst formation in vitro and in vivo but did not affect the induction of a robust IgG response in mice. We propose that our protocol can be used to study the contribution of the humoral immune response to rodent behavioral alterations following T. gondii infection.

Delay-induced oscillatory dynamics in humoral mediated immune response with two time delays

A mathematical model for the quantitative analysis of cancer immune interaction, considering the role of humoral (antibody) mediated immune response with two time delays, namely maturation and interaction delays has been proposed in this paper. The aim of this work is to assess the effect of time delays on the interaction between cancerous cells and the antibodies. After categorizing the parametric plane into different regions based on the existence of equilibria, we investigate both analytically and through simulations, the stability of equilibria and the onset of sustained oscillations through Hopf bifurcations. The direction and stability of the Hopf bifurcation which occurs at the positive interior equilibrium point of the system have also been studied. It is observed that both the delays play an important role in stability switching. Appropriate therapy with a proper choice of system parameters are suggested to obtain cancer free equilibrium.

Abstract 5364: Correlation of immune responses and overall survival in a phase II study of belagenpumatucel-L, an allogeneic tumor cell vaccine, in non-small cell lung cancer (NSCLC)

Abstract This study examines the correlative/predictive value of cellular- and humoral-mediated immune response on the clinical responsiveness of patients who received belagenpumatucel-L, a therapeutic vaccine comprised of 4 TGF-β2 antisense gene-modified allogeneic non-small cell lung cancer (NSCLC) cell lines in a phase II clinical trial in which subjects with stage III/IV NSCLC received intradermal injections of the vaccine every 4-8 weeks. We performed assays of cellular (ELISPOT) and humoral (antibody ELISA) immunity on 36 subjects in the trial and correlated these data with the long term assessment of overall survival. All but one subject in the study showed an increase in immune reactivity in at least one of the cellular or humoral assays. Eleven subjects who demonstrated an aggregate increase in both cellular and humoral immune reactivity (positive by three of four criteria tested) had a median survival of 32.5 months (95% CI, 25.2 to 39.8). This was significantly better than the median survival of only 11.6 months (95% CI, 5.6 to 17.6) for the 25 subjects who showed an increase in one or none of the measured immune parameters (p=0.015, log-rank test). The demonstration of a statistically significant correlation between cellular and humoral immune responses and overall survival in subjects treated with belagenpumatucel-L suggest that both compartments of the immune system likely impact the clinical response and are important for the induction of clinically significant antitumor immunity by the vaccine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5364. doi:1538-7445.AM2012-5364

Dual Strategy for Immune Defense in the Land SnailCornu aspersum(Gastropoda, Pulmonata)

Immune defenses have been shown to be heavily involved in the evolution of physiological trade-offs. In this study, we compared the internal defense systems in two subspecies of the land snail Cornu aspersum that exhibit contrasting life-history strategies. The "fast-living" Cornu aspersum subsp. aspersa is widespread throughout the world, especially in ecosystems disturbed by man, whereas natural populations of the giant Cornu aspersum subsp. maxima, characterized by a longer life span, are present only in north Africa. Snails were experimentally challenged with Escherichia coli; the measurements used to assess their internal defense for cell- and humoral-mediated immune responses were bacterial clearance, hemocyte density, reactive oxygen species (ROS) production, and plasma antibacterial activity. Both subspecies showed a similar ability to clear bacteria from their hemolymph; however, they varied in the robustness of different individual immune components. Cornu aspersum aspersa had higher ROS activity than did C. a. maxima and lower plasma bactericidal activity. These results suggest that ecological factors can sculpt the immune response. One interpretation is that shorter life span selects for immune defenses such as ROS that, although effective, can cause long-term damage. Such different immune patterns obviously entail various costs involved in the strong intraspecific variation of life-history trade-offs we previously observed. We also have to consider that such variation might be related to intraspecific differences in the relative strength of resistance and tolerance mechanisms.

Cytokine Alteration Following Antioxidant Supplementation And Anterior Cruciate Ligament Surgery

Vitamins E and C display immuno-modulatory properties. Cellular and humoral mediated immune responses are associated with T helper 1 (Th1) and Th2-type cytokines, respectively. Balance disruptions to the interleukin (IL)-6:IL-10 and Th1:Th2-type cytokine ratios indicate a shift in pro-/anti-inflammatory and pattern of adaptive immunity cytokine dominance, respectively. Furthermore, disruptions to the IL-6:IL-10 ratio may provide prognostic potential following severe trauma or surgery. Interleukin (IL)-10 is an anti-inflammatory cytokine that suppresses pro-inflammatory (i.e., TNF-a, IL-1, IL-6, etc.) and Th1-type (i.e., IL-2, IL-12, IFN-γ) cytokines. IL-10 increases during the reperfusion following anterior cruciate ligament (ACL) surgery, which we found is ameliorated with vitamin E and C supplementation. PURPOSE: To identify the influence of vitamins E and C on the IL-6:IL-10 ratio, and Th1- (IFN-γ, IL-2, IL-12) - Th2- (IL-4, IL-5, IL-10) type cytokine ratios following ACL surgery. METHODS: A randomized, double-blind, placebo-controlled study was carried out in men undergoing ACL reconstructive surgery, who were randomly assigned to twice daily supplementation with either: 1) antioxidant (AO; 300 mg RRR-a-tocopheryl acetate (400 IU) and 500 mg ascorbic acid (AA), n = 13), or 2) matching placebos (PL; n = 12). Experimental treatment began ∼2-wks prior and continued through 7-d post-surgery. Subjects provided fasting blood draws: 1) Baseline (Bsl, ∼2 wk prior to surgery), 2) pre-surgery (Pre, ∼90-min pre-surgery), 3) 90-min, 4) 72-h and 5) 7-d post-surgery. Plasma a- and γ-tocopherols (a- and γ-T), AA, cytokines, and serum high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS: Following AO supplementation, circulating a-T and AA increased, while γ-T decreased (P < 0.05; treatment X time interaction). Both IL-6 and hsCRP were elevated at 72-h and 7-d (P < 0.05). Interestingly, depressions in the IL-6:IL-10, IFN-γ:IL-10 and IL-2:IL-0 ratios following ACL surgery were ameliorated with AO supplementation (P < 0.05; treatment X time interaction). CONCLUSION: Moderate supplementation levels of vitamin E and C minimize the depression in the IL-6:IL-10, IFN-γ:IL-10 and IL-2:IL-10 ratios post-ACL surgery.

Arginine and Vitamin E improve the antibody responses to infectious bursal disease virus (IBDV) and sheep red blood cells in broiler chickens

1. Dietary arginine (ARG) and vitamin E (VE) have been shown to improve immune responses in broiler chickens, but their combined effects have not been well documented. The objective of this study was to evaluate the combined effects of dietary ARG and VE on antibody responses to sheep red blood cell (SRBC, agglutination assay) inoculation in 13-d-old chicks, and antibody titres (ELISA) to infectious bursal disease virus (IBDV) before and after vaccination of 20-d-old chicks. 2. One-day-old broiler chicks were fed diets with normal (NARG, 12 g/kg of feed) or high (HARG, 22 g/kg of feed) inclusion rates of ARG, and three rates of VE (40, 80, or 200 mg/kg of feed; 40 mg being the supplement used in commercial diets) in a factorial arrangement. 3. Antibody titres to SRBC at 5, 8, and 12 d after inoculation were higher in chicks fed on the HARG diet than in those on NARG, and in chickens on VE80 compared with those on VE200 at 5, 8, and 12 d after inoculation. Antibody titres to the IBDV 2 days before and 19 d after vaccination were higher in chickens on HARG compared with those on NARG, and in chicks on VE80 compared to those on VE40 but similar to those on VE200. Conversely, 5 d after vaccination titres against IBDV were higher in chicks on NARG than in those on HARG, and in chickens on VE40 compared with those on VE80, yet similar to those on VE200. 4. These results show that diets with high ARG and high VE (80 mg/kg) improved the humoral-mediated immune response of broilers to IBDV and SRBC, suggesting it could be a strategy to improve vaccination protection and resistance to diseases.