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PubMed2004

Nutritional modulation of immune function in broilers.

Collaborative research efforts across disciplines typically result in more insight toward the hypothesis being tested due to the omnibus nature of the projects. For example, nutritional experiments evaluating a nutrient response will benefit greatly by incorporating biochemical, physiological, and immunological endpoints for measurement. Clearly, commercial poultry producers do not have the luxury of focusing on specific disciplines when field problems occur. Hence, in practice interplay exists among nutrition, genetics, management, and diseases. Dietary composition impacts immune function of the chicken. As research in the area of nutritional immunology has increased, it is becoming apparent that nutrient needs for immunity do not coincide with those for growth or skeletal tissue accretion. This review is not a comprehensive assessment of nutrient needs for immunity in the chicken. Rather, this review is concerned with nutritional modulation of immunity in broilers that offers insight for nutritionists and researchers to implement nutritional regimens to reduce the severity of disease and to test or validate nutritional regimens that heighten immunity. Nutritional modulation of the hen diet and in ovo nutrient modulation to improve chick immunity and disease resistance are discussed.

Amino Acids↗

PubMed2004

Prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis modulates intestinal immune functions in rats.

Probiotics (PRO) modulate systemic immunity in animals and humans. In contrast, the effects of prebiotics (PRE) on systemic and intestinal immunity have not been investigated. Whether the combined application of PRO and PRE [synbiotics (SYN)] has synergistic or additive effects is presently unknown. Therefore, PRO (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12), PRE (inulin enriched with oligofructose), and SYN (combination of PRO and PRE) were fed to F344 rats for 4 wk as supplements to a high fat diet. Functions of immune cells isolated from peripheral blood mononuclear cells (PBMC), spleen, mesenterial lymph nodes and Peyer's patches (PP) were investigated. The SYN supplement increased secretory immunoglobulin A (sIgA) production in the ileum compared with controls fed the high fat diet alone (P<0.05), and decreased the oxidative burst activity of blood neutrophils (P<0.05) compared with rats fed PRO. The PRE supplement enhanced the production of interleukin-10 (P<0.05) in PP as well as the production of sIgA in the cecum (P<0.05), compared with controls. The PRO supplement modestly affected immune functions, whereas systemic immunomodulatory effects were observed in rats fed SYN. The PRE supplement primarily acted at the level of the gut-associated lymphoid tissue. The combined application of PRO and PRE has different effects from those of the individual supplements, but does not simply result in additive or synergistic effects.

Animals↗

PubMed2004

Intestinal immunity of rats with colon cancer is modulated by oligofructose-enriched inulin combined with Lactobacillus rhamnosus and Bifidobacterium lactis.

Probiotics (PRO) are known to modulate immunity in animals and human subjects and to inhibit colon carcinogenesis in experimental models, but the effects of synbiotics (SYN) are not well understood. Therefore, the effects of PRO (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12), PRE (inulin-based enriched with oligofructose, 100 g/kg) and SYN (combination of PRO and PRE) on the immune system of rats were investigated in the azoxymethane (AOM)-induced colon cancer model. After 33 weeks, rats with and without AOM treatment were killed and immune cells were isolated from spleen, mesenterial lymph nodes (MLN) and Peyer's patches (PP). AOM treatment significantly reduced natural killer (NK) cell-like cytotoxicity in control rats and in PRO- and PRE-supplemented rats. SYN supplementation prevented the AOM-induced suppression of NK cell-like cytotoxicity in PP compared with control rats (P<0.01). SYN and PRE supplementation stimulated IL-10 production in PP in these rats (P<0.01) and in MLN of rats not treated with AOM (P<0.05). Interferon-gamma production in PP was decreased by PRO supplementation (PRO and SYN groups combined; P<0.05). Proliferative responsiveness of lymphocytes (PP) from AOM-treated rats was suppressed in SYN-supplemented rats (P<0.01). Overall, SYN supplementation in carcinogen-treated rats primarily modulated immune functions in the PP, coinciding with a reduced number of colon tumours. PRE and PRO provided in combination as SYN may contribute to the suppression of colon carcinogenesis by modulating the gut-associated lymphoid tissue.

Animals↗

PubMed1991

[Effect of leu-enkephalin in striatum on modulating cellular immune during electropuncture].

Zusanli points of rat were used to study the effect of acupuncture on the synthesis and release of endogenous leu-enkephalin (LEK) in modulating immune function as assayed by T lymphocyte proliferative response, i.e. the lymphocyte transformation test (LTT). The results are as follows: (1) LEK level in striatum was increased as LTT was enhanced by puncture. The latter effect could be inhibited by microinjection of naloxone into striatum. (2) Injection of LEK into striatum caused a significant enhancement of LTT, an effect being more powerful than did by electropuncture. (3) Following injection of LEK antiserum into striatum, electropuncture enhanced LTT was inhibited. The above results demonstrate that the LEK plays an important role in modulating cellular immune function during electropuncture, through its action in striatum either as a neurotransmitter or as a neuromodulator.

Animals↗

PubMed1976

Effects of contact sensitization and delayed hypersensitivity reactions on immune responses to non-related antigens. Modulation of Immune responses.

Guinea pigs were immunized intracutaneously into the ears with sheep red blood cells (SRBC). Application of a sensitizing dose of the contact allergen dinitrochlorobenzene (DNCB) onto the same ears was shown to suppress or enhance the humoral response to SRBC depending on the time of application. When guinea pigs were sensitized to a contact allergen, application of a sensitizing dose of a non-related allergen on the same ears either had no effect or caused a clear enhancement of the development of delayed type hypersensitivity (DTH). Strongest enhancement was found when both sensitizations were performed on the same day. Further experiments on the effects of a concomitant DTH reaction elicited at the site of application of a contact allergen showed a strong potentiation of DTH when B-cell suppression was minimized by pretreatment with cyclophosphamide (CY). It was considered that CY-DTH-immunopotentiation might be a useful tool for achieving a higher level of sensitivity after epicutaneous sensitization.

Allergens↗

PubMed1979

Improved immunosuppression for cardiac transplantation: immune monitoring and individualized modulation of recipient immunity by in vitro testing.

These studies demonstrate that immune monitoring and individualized modulation of recipient immune reactivity using a quality-controlled preparation of rabbit antithymocyte globulin can improve results of cardiac transplantation. The most valuable assay in individualizing drug doses was the serial measurement of T-cell levels using a complete lymphocyte profile technique and monitoring with phytohemagglutinin to rule out false low T-cell levels. Using this system, the incidence and severity of early rejections were markedly reduced and no grafts were lost to rejection in the first month. The recent first-year graft survival has been about 60%, an improvement largely related to a reduction in early rejection and infection. This technique of immunosuppression appears quite promising for improving the results of future cardiac transplantations.

Antilymphocyte Serum↗

PubMed2002

Prolactin modulation of immune and inflammatory responses.

Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse physiological functions via its effects on cellular processes such as proliferation, differentiation, and cell survival. All these activities are mediated by the PRL receptor (PRL-R), a member of the hematopoietin cytokine receptor superfamily. To understand PRL-dependent mitogenic signaling in T cells, we cloned PRL. PRL-R, one mediator of PRL signaling, signal transducer and activator of transcription (Stat) 5b, and a panel of PRL-inducible immediate early-response genes from T cells. We are employing one of these PRL-inducible genes, the transcription factor interferon regulatory factor-1 (IRF-1), a multifunctional immune regulator gene, as a tool to understand how PRL modulates T-cell proliferative responses. In investigating regulatory events along the PRL-R/Janus activating kinase (JAK)/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross talk between Stat and nuclear factor (NF)kappaB signaling pathways also regulates IRF-1 expression. In understanding how signaling pathways cross talk at the IRF-1 promoter, we obtained insights into how PRL can modulate immune and inflammatory responses. These findings have much broader implications, not only for cells in the immune system but also for other PRL-responsive cells and tissues.

Animals↗

PubMed1999

Altering the cellular location of an antigen expressed by a DNA-based vaccine modulates the immune response.

The potential for DNA vaccines encoding mutated versions of the same antigen to modulate immune responses in C3H/HeN mice was investigated. We created expression plasmids that encoded several versions of glycoprotein D (gD) from bovine herpesvirus 1, including authentic membrane-anchored glycoprotein (pSLRSV.AgD), a secreted glycoprotein (pSLRSV.SgD), and an intracellular protein (pSLRSV.CgD). Immunization of an inbred strain of mice with these plasmids resulted in highly efficacious and long-lasting humoral and cell-mediated immunity. We also demonstrated that the cell compartment in which plasmid-encoded gD was expressed caused a deviation in the serum immunoglobulin (Ig) isotype profile as well as the predominant cytokines secreted from the draining lymph node. Immunization of C3H/HeN mice with DNA vaccines encoding cell-associated forms of gD resulted in a predominance of serum IgG2a and gamma interferon-secreting cells within the spleens and draining lymph nodes. In contrast, mice immunized with a secreted form of this same antigen displayed immune responses characterized by greater levels of interleukin 4 in the draining lymph node and IgG1 as the predominant serum isotype. We also showed evidence of compartmentalization of distinct immune responses within different lymphoid organs.

Animals↗

PubMed2003

Oxidised LDL modulates immune-activation by an IL-12 dependent mechanism.

Oxidised low density lipoprotein (oxLDL) is one factor that may cause the immune reaction in the artery wall characteristic of atherosclerosis. OxLDL can promote immune activation as determined by enhanced secretion of IFN-gamma and TNF by immune competent cells. We previously demonstrated that Platelet-activating factor (PAF)-like lipids and/or lysophosphatidylcholine (LPC) in OxLDL contribute significantly to this immune activation, but these factors may also inhibit immune activation, at higher concentrations. We here demonstrate that IL-12 induces enhanced IFN-gamma secretion in peripheral blood mononuclear cells (PBMC), with no addition of a specific antigen, as determined by ELISPOT. Antibodies to IL-12 and to MHC class II inhibited both IL-12- and oxLDL-induced IFN-gamma secretion. OxLDL induced IL-12 production in PBMC. In the presence of IL-10, a T helper 2 cytokine, oxLDL induced a decreased IFN-gamma secretion, indicating that the local cytokine-milieu may determine the immunological properties of oxLDL. IL-10 could also be induced by OxLDL. Mononuclear leukocytes were prepared directly from human atherosclerotic plaques obtained at carotid operations. OxLDL had the capacity to induce IL-12, IL-10 and TNF from plaque cells using ELISPOT. Taken together, our data indicate that oxLDL can modulate immune reactivity in atherosclerosis by a nonspecific mechanism. OxLDL can be inhibitory, especially at higher concentrations. However, oxLDL can also promote immune activation by functioning as an adjuvant, potentiating and/or modulating immune-reactions via IL-12 and other cytokines including IL-10. This suggests that a specific T cell epitope in oxLDL is not necessary for oxLDL-induced T cell activation.

Adjuvants, Immunologic↗

PubMedDate not supplied

Effective monitoring and modulation of immune reactivity in allograft recipients.

This study demonstrates that current techniques of immune monitoring and modulation are available, which have potential to reduce early cadaver allograft loss from rejection to 5% or less. The techniques center on the monitoring of T lymphocyte levels and T lymphocyte reactivity, using relatively simple and reproducible assays, which give results within 4-72 hrs, depending upon the tests used. In addition, these techniques include modulation of T cell levels and reactivity using quality-controlled anti-thymocyte globulin (ATG) in low doses during the post-transplant period. High potency ATG demonstrates a significant capability of preventing early (3 mos) graft rejection, as well as maintaining low levels and reactivity of T cells for 3 mos or longer, when intermittent low dose therapy is utilized. Evidence is presented that ATG has a relatively selective effect on T lymphocytes and this may result in a degree of selective immunosuppression not achieved in clinical transplantation to date.

Antilymphocyte Serum↗

PubMed1985

The modulation of immune complex aggregation by classical pathway-mediated reactions.

Classical pathway (CP)-triggered reactions of complement-modulated immune complex (IC) aggregation (tetanus toxoid/human anti-tetanus toxoid-IgG; ICs of equivalence) were investigated turbidimetrically during the early stages of reaction. Monospecific Fab'- or Fab-fragments (rabbit) directed against certain complement components were used to block the complement function in normal human serum (NHS). Additionally, parts of the reactions were studied using purified complement components. C1q in serum generated by the addition of EDTA as well as purified C1q were found to increase the IC aggregation. In contrast to C1q, macromolecular C1 is able to inhibit IC aggregation, whereas additional participation of C-1 INH reversed this process. The cooperation of the remaining CP proteins (C4, C2, C4bp, and I) reconstituted the inhibition capacity of the complement. Whereas C3 supported significantly inhibition, a significant influence of other effector pathway (EP) components (C5-C9) was not detectable turbidimetrically.

Antigen-Antibody Complex↗

PubMedDate not supplied

Is the use of specialized nutritional formulations a cost-effective strategy? A national database evaluation.

BACKGROUND: We apply currently published clinical outcomes data to length of stay and hospital cost to determine the potential economic benefit associated with the use of specialized nutritional formulations in elective surgical, trauma, and medical patients. Although the use of immune-modulating formulations has repeatedly shown favorable clinical outcomes, including decreased complications (both infectious and noninfectious), length of stay (both ICU and total days), and ventilator days, the cost-effectiveness of nutritional modulation of the immune response in a US-based population has not previously been explored. METHODS: Data for the current study were obtained from a large national database with 126 member hospitals and data from over 1 million patients. Data extracted from the database included patient type (surgical, medical, and trauma) and subservice, whether the hospital stay was "complicated" or "uncomplicated" (as determined by diagnosis-related groups and International Classification of Diseases, Ninth Revision coding), mean length of stay, mean cost, and incremental cost per complication experienced. The clinical outcomes measures from 3 major peer-reviewed studies were then applied to the cost data in order to determine the cost savings associated with the use of specialized nutritional formulations in each of the patient populations. Additionally, cost data were segmented by region of the United States (New England, mid-Atlantic, South, Midwest, Southwest, and West) and by primary focus of the health care facility (academic, indigent care, large community) to enable more meaningful cost comparisons. RESULTS: For the medical patient population, according to the published rate of 51% decrease in risk of infectious complications and a decreased length of hospital stay of 9.7 days, net cost savings (after accounting for the increased costs of administering immune modulating formula) is $2066. The same calculations were done for surgical and trauma patients, with $688 and $308 net cost savings per patient, respectively. These figures assume a base infection rate of 5%. Expected cost savings vary markedly for deviations in base infection rate and slightly for differences in facility type or region of the country. CONCLUSIONS: This study demonstrates that specialized nutritional formulations are a cost-effective way for hospitals to improve clinical outcomes while reducing resource consumption and total cost. These benefits are observable in all patient types, all facility types, and all regions of the United States.

Cost-Benefit Analysis↗

PubMed2026

The role of KIAA1467 in breast cancer: insights from pan-cancer and single-cell sequencing analysis.

BACKGROUND: Improving the response rate of single-agent immune checkpoint blockade (ICB) urgently requires the discovery of new therapeutic targets for combinatorial regimens. Analyses of tumor microenvironment (TME)-associated biomarkers have verified that KIAA1467 drives the formation of an immune-excluded, non-inflamed TME in breast cancer (BRCA). This study systematically explores the expression pattern, prognostic value, immune regulatory function, biological effects, and drug resistance relevance of FAM234B (also known as KIAA1467) in BRCA. METHODS: We performed pan-cancer survival analysis using The Cancer Genome Atlas (TCGA) datasets. Multi-omics bioinformatics analyses were conducted to evaluate KIAA1467 expression across malignancies. Single-cell RNA sequencing (scRNA-seq) data from GSE176078 was utilized to localize KIAA1467 expression at the cellular level. Immunohistochemistry and western blot assays validated KIAA1467 expression in BRCA clinical specimens. Correlation analyses were implemented to assess relationships between KIAA1467 expression, clinicopathological features, immune modulators, tumor-infiltrating immune cells, and p53 mutation status. Functional enrichment analysis uncovered relevant signaling pathways. Bioinformatic half maximal inhibitory concentration (IC50) prediction and in vitro cellular experiments were applied to evaluate associations between KIAA1467 and chemotherapeutic drug sensitivity. RESULTS: TCGA pan-cancer survival analysis demonstrated that elevated KIAA1467 expression significantly predicted shortened overall survival in BRCA and multiple other tumor types. KIAA1467 displayed distinct expression patterns across cancers, with prominent upregulation in BRCA. scRNA-seq confirmed enriched KIAA1467 expression within BRCA cells, and its upregulation in BRCA tissues was further verified by immunohistochemistry and western blot. High KIAA1467 expression was positively correlated with advanced tumor grade and lymphatic metastasis. KIAA1467 showed negative correlations with most immune modulators and core immune checkpoint molecules, as well as tumor-infiltrating immune cells in the TME, implying its potential function in tumor immune evasion. Low KIAA1467 expression was tightly linked to p53 mutations. Enrichment analysis indicated participation of KIAA1467 in epithelial-mesenchymal transition, apoptosis and cell cycle arrest. Furthermore, high KIAA1467 expression corresponded to higher estimated IC50 values of cisplatin, gefitinib, paclitaxel and gemcitabine, consistent with reduced chemosensitivity observed in vitro. CONCLUSIONS: This study reveals the multifaceted oncogenic role of KIAA1467 in BRCA. KIAA1467 participates in remodeling an immunosuppressive TME, correlates with malignant progression and chemoresistance, and may serve as a promising candidate target to optimize ICB-based combination therapy for BRCA. These findings offer new perspectives for the clinical treatment and comprehensive management of BRCA.

KIAA1467↗

PubMed1994

Modulation of immune reactivity by unilateral striatal and mesolimbic dopaminergic lesions.

Asymmetrical modulation of immune reactivity by central dopaminergic pathways was suggested by previous reports which described an association between alterations of immune response and peculiar patterns of dopamine asymmetries in pathological and physiological situations. In the present experiments, we studied the respective roles of the nigrostriatal and mesolimbic dopaminergic networks in the asymmetrical modulation of immune responses. Lymphocyte proliferation as well as natural killer (NK) cell activity were analysed in mice, 2 weeks after unilateral lesions of dopaminergic projections by in situ injection of 6-hydroxydopamine in the striatum or the nucleus accumbens. After lesions of the striatum, proliferation of splenic lymphocytes was impaired only in the right-lesioned group. Left-lesions appeared to not modify T lymphocyte reactivity. After lesions of the nucleus accumbens, no modification of T lymphocyte mitogenesis was observed but splenic NK cell activity was depressed in left-lesioned mice as compared with controls or right-lesioned animals. Proliferation of B lymphocytes was not affected by striatal or mesolimbic dopaminergic lesions. It was concluded that both striatal and mesolimbic dopaminergic pathways are asymmetrically involved in neuro-immunomodulation. These dopaminergic regions appear to function independently as the effective side as well as the immune parameters that were altered differ according to the structure lesioned.

Animals↗

PubMed2005

The impacts of the "Immune of Life" for teens module application on the coping behaviors and mental health of early adolescents.

This quasi-experimental research is the subsequent part of the Health Promotion for Early Adolescents Project, which focuses on the training of schoolteachers in using the module Immune of Life for Teens, which was developed in 1999, for evaluating its impact. The module consists of a manual and a VDO cassette display of a story of a teenager who has difficulty adjusting to life changes. The program aimed at improving the coping skills and psychological health or mental health of junior high school students. Schoolteachers from 13 schools participated nationwide as part of an experimental group and received training in the use of the module in their schools with students in Grades 7-9. The control group was composed of 3 schools that did not apply the module. Each school performed the pretest and posttest 1 month after the module's application. The total number of the students in the study was 1,580. There were 445 students in the control group, 474 in the experimental I group (intensive training) group, and 661 in the experimental II group (nonintensive group). The instruments used to evaluate impact were the following: (1) Young Adult Coping Orientation for Problem Experiences, which was developed by Patterson, McCubbin, and Grochowski in 1983, and the (2) Thai Mental Health Questionnaire, a 70-item self-administered questionnaire developed by Pattrayuwat in 1999 to assess mental health status. The findings reveal that both experimental groups had better coping behaviors than the control group when using pretest scores as covariates (experimental I group: F = 9.425, p < .01; experimental II group: F = 22.446, p < .001) 1 month after the module was implemented. They also show that both experimental groups had better mental health than the control group when using pretest scores as covariates (experimental I group: F = 6.034, p < .05; experimental II group: F = 6.596, p < .001) 1 month after the module was implemented. The study confirmed the impact of the Immune of Life for Teens module on better coping behaviors and better mental health status among the subjects after it was implemented by their teachers. Thus, for further use of the module, intensive training for schoolteachers is recommended for the health promotion of early adolescents.

Adaptation, Psychological↗

PubMed2004

Regulation of allergy and autoimmunity in helminth infection.

Parasitic infections are a major theme in the "hygiene hypothesis", as allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms. Helminths"-the grouping of multicellular worm parasites including nematodes, cestodes and trematodes-tend to establish long-lived, chronic infections indicating successful down-modulation of the host immune system. In this review, we describe the intricate immunology of host-helminth interactions and how parasites manipulate immune responses to enhance their survival. In so doing, they often minimise immunopathology and, it is suggested, reduce host susceptibility to, and severity of allergic and autoimmune diseases. Studies on helminth-infected communities and individuals support the hypothesis that an immuno-regulatory network promoted by parasites extends its influence to limiting allergies. Experimental models are now probing more deeply into the area of immune modulation by helminths, and we discuss the likely mechanisms by which helminths could be establishing a strongly regulatory environment. Understanding and harnessing the modulatory capacity of helminths may uncover novel therapeutic interventions, mimicking and exploiting their evolution for our benefit. Parasitic infections are a major theme in the "hygiene hypothesis", as allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms. Helminths"-the grouping of multicellular worm parasites including nematodes, cestodes and trematodes-tend to establish long-lived, chronic infections indicating successful down-modulation of the host immune system. In this review, we describe the intricate immunology of host-helminth interactions and how parasites manipulate immune responses to enhance their survival. In so doing, they often minimise immunopathology and, it is suggested, reduce host susceptibility to, and severity of allergic and autoimmune diseases. Studies on helminth-infected communities and individuals support the hypothesis that an immuno-regulatory network promoted by parasites extends its influence to limiting allergies. Experimental models are now probing more deeply into the area of immune modulation by helminths, and we discuss the likely mechanisms by which helminths could be establishing a strongly regulatory environment. Understanding and harnessing the modulatory capacity of helminths may uncover novel therapeutic interventions, mimicking and exploiting their evolution for our benefit.

Animals↗

PubMed1983

Immunization with idiotypic immunoglobulin protects against development of B lymphocytic leukemia, but emerging tumor cells can evade antibody attack by modulation.

Immunization of strain 2 guinea pigs with idiotypic IgM obtained from serum of animals in the terminal phase of the L2C leukemia produced high levels of circulating anti-idiotypic antibody that was cytotoxic for the tumor cells in the presence of syngeneic C. Such animals showed good protection against injected tumor cells, but after a long delay, leukemia did develop. As tumor cells appeared in the blood, anti-idiotype was consumed, but the cells displayed little or no surface Ig and could not be killed in vitro by anti-idiotype and C. However, as serum antibody levels fell, the cells displayed increasing amounts of surface IgM lambda of the same idiotype and regained their susceptibility to the antibody and C in vitro. It appears, therefore, that the ability of tumor cells to modulate their target idiotype can present a considerable problem for antibody-mediated attack.

Animals↗

PubMed2003

Intranasal immunotherapy is more effective than intradermal immunotherapy for the induction of airway allergen tolerance in Th2-sensitized mice.

Immunotherapy (IT) by injection more readily induces clinical tolerance to stinging insects than to respiratory allergens. However, while systemic immunization induces adaptive responses systemically, the induction of mucosal immunity generally requires local Ag exposure. Taken together, these observations suggest that the poor success rate of systemic IT for asthma could be a consequence of inadequate immune modulation in the airways. In support of this position, investigations presented in this report demonstrate that allergen IT more effectively induces airway allergen tolerance in Th2-sensitized mice, when delivered by the intranasal (i.n.) vs the intradermal (i.d.) route. Moreover, compared with native allergen, allergen immunostimulatory sequence oligodeoxynucleotide conjugate proved to be a more effective i.n. IT reagent for protecting allergic mice from airway hypersensitivity responses. Furthermore, for both native allergen and allergen immunostimulatory sequence oligodeoxynucleotide conjugate, i.n. and i.d. IT delivery were similarly effective in modulating systemic immune profiles in Th2-sensitized mice, while only i.n. IT had significant immunomodulatory activity on B and T cell responses in the airways. The present investigations may be the first to suggest that i.n. IT is more effective than i.d. IT for the treatment of asthma. Furthermore, our results suggest that modulating airway rather than systemic immunity may be the more important therapeutic target for the induction of clinical tolerance to respiratory allergens.

Adjuvants, Immunologic↗