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Results for “host response”

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At least 199 records · Page 11Linked to original sources

PubMed2005

TX-1877, a bifunctional hypoxic cell radiosensitizer, enhances anticancer host response: immune cell migration and nitric oxide production.

We investigated in the current study the effect of TX-1877, a bifunctional hypoxic cell radiosensitizer, in augmenting anticancer host response. In the syngeneic squamous cell carcinoma-bearing mouse model, a single administration of TX-1877 significantly inhibited the primary tumor growth as well as lung metastasis. TX-1877 administration resulted in a significant infiltration of immune cells, such as CD4+T, CD8+T cells, macrophages and dendritic cells (DCs), and an increased expression of chemokines for cytotoxic T lymphocytes (CTLs), helper T-cell 1 (Th1) cells, monocytes/macrophages and DCs, in tumor tissues. Nitric oxide (NO) production and the expression of inducible NO synthase (iNOS) and interferon-gamma, a major Th1 cytokine that plays a major role in anticancer immunity, were also enhanced. Furthermore, neutralization of NO by N-monomethyl-L-arginine acetate resulted in a marked inhibition of the antitumor effect of TX-1877. In tumor-draining lymph nodes, MHC class I-restricted CD8+ memory CTLs specific for inoculated cancer cells were induced by TX-1877. In in vitro experiments, TX-1877 induced chemokines and iNOS/NO in several types of culture cells. These findings strongly suggested that TX-1877 induces migration of CD8+CTLs, CD4+Th1 cells, macrophage/monocytes and dendritic cells into the tumor site, and that this migration is mediated by chemokine induction. In addition, it was suggested that NO produced by several types of cells stimulated by TX-1877 in the tumor sites plays a major role in the anticancer effect of TX-1877. TX-1877 was thus shown to be an effective immunopotentiator as well as a hypoxic cell radiosensitizer.

Animals↗

PubMed1987

Mouse candidiasis. II. Host responses are T-cell dependent and regulated by genes in the major histocompatibility complex.

Administration of a Thy-1.2-specific monoclonal antibody to BALB/c mice resulted in a significant decrease in the efficiency of clearance of Candida albicans from the spleen. The rate of clearance of organisms from the spleen of congenic mice was determined by genes in the major histocompatibility complex, as was the magnitude of the inflammatory response in the popliteal lymph node after footpad immunization. These results formally demonstrate the involvement of T cells in host responses to primary candida infection.

Animals↗

PubMed1998

Development of a novel in vitro co-culture system for studying host response to native bacterial antigens.

We have developed a novel co-culture system in which murine splenocytes are cultured with live bacteria in the presence of a bacteriostatic antibiotic. Superantigens, like staphylococcal enterotoxin B (SEB) are important factors in bacterial pathogenicity. Research has shown that superantigens affect numerous immune cell types, either directly or indirectly, yet their involvement in pathogenic mechanisms remains poorly defined. In these studies, we utilize the co-culture system to study how superantigen pretreatment affects interferon-gamma (IFN-gamma) production by splenocytes co-cultured with gram-positive bacteria. Streptococcus mutans, S. sanguis and Bacillus subtilis were tested for susceptibility to a panel of antibiotics. Spectinomycin was found to maintain a bacteriostatic state of approximately 10(5) bacteria ml(-1) at optimal concentrations for each bacterial strain. Co-culturing splenocytes with bacteria did not affect splenocyte viability and cultured splenocytes responded to mitogenic stimulation as expected. Two days after SEB pretreatment, isolated splenocytes cultured with either Streptococcus species produced 10-15 times more IFN-gamma than splenocytes from sham-injected controls; however, no differences in CD4+ or CD8+ T cell populations appeared in cultures with or without bacteria. Splenocytes isolated four days after SEB treatment did not produce significant amounts of IFN-gamma in co-culture. Co-cultures containing live bacteria produced four times more IFN-gamma than cultures containing heat-killed bacteria. Splenocytes depleted of natural killer (NK) cells prior to SEB treatment produced 25% less IFN-gamma after 20 h co-culturing with S. mutans. T lymphocytes were identified to be the major producer of IFN-gamma at this time point by intracellular cytokine staining. Apparently SEB exposure primes a response to live bacteria and the response is evident two days after initial exposure. The in vitro co-culture system allows us to observe host responses to bacteria in the context of the multicellular interdependent immune response. With this assay we can more closely 'mimic' in vivo events, particularly immune cell interactions in microfloral environments, to study how the pathogenic effects of superantigens alter this response.

Animals↗

PubMed1987

Endothelial cell procoagulant properties and the host response.

These studies of endothelial cell coagulant properties indicate the potentially active role of endothelium in the modulation of procoagulant and anticoagulant mechanisms. In addition, they draw attention to the different types of mechanisms that function in the maintenance of hemostasis and the induction of thrombosis. Hemostasis requires a rapid and complete response to injury in order to serve the host effectively; the optimal response to a penetrating injury involves rapid formation of a thrombus to prevent extravasation and maintain hemodynamics. In contrast, thrombosis could involve a more subtle and gradual modulation of cellular coagulant properties. An inflammatory mediator such as interleukin 1 could shift vessel wall coagulant properties over hours, and when coupled with an additional stimulus, such as perturbation of blood flow, could result in thrombus formation. The latter clot would form on a morphologically intact but functionally altered endothelium. Perturbation of endothelial cell coagulant properties by physiologic mediators of the host response may provide insights into mechanisms through which the vessel wall can contribute to the pathogenesis of thrombotic disease.

Animals↗

PubMed1995

Host response to multiple skin lacerations on the albino guinea pig.

Investigators have studied methods of treating skin lacerations by placing multiple incisions on each albino guinea pig. Theoretically, host responses to laceration sites may differ on the basis of anatomic location and local cytokine effects. We used cytokine values and histologic examination to identify differences when multiple lacerations were placed on each animal. Four 3-cm lacerations were made on the dorsum of each male albino guinea pig: two incisions on either side and parallel to the spine. Each laceration was closed with staples. In five animals a sponge technique was used to assay wound cytokines 48 h later. In an additional four animals, wounds were excised at 96 h and stained for cells and new collagen. We identified no statistically significant differences among laceration sites based on polymorphonuclear and mononuclear cellularity, number of fibroblasts, new collagen deposition, or wound interleukin (IL)-6 activities. Using this model minimizes the number of animals needed to generate statistically significant findings in wound research.

Animals↗

PubMed2001

Host responses and persistence of vector genome following intrabronchial administration of an E1(-)E3(-) adenovirus gene transfer vector to normal individuals.

Adenovirus (Ad)-mediated gene transfer to the respiratory epithelium of experimental animals and to nasal and airway epithelium of individuals with cystic fibrosis is followed by transient gene expression. Extensive studies in experimental animals are consistent with the concept that local cellular host anti-vector immune responses account for this short-term expression, and systemic and local [lung epithelial lining fluid (ELF)] anti-Ad neutralizing antibodies are generated following Ad vector administration to the respiratory epithelial surface. To determine if this paradigm holds in normal humans, a first-generation Ad vector (Ad(GV)CD.10, an E1(-)E3(-) Ad serotype 5-based vector coding for the Escherichia coli cytosine deaminase gene) was sprayed locally in escalating doses (8 x 10(8)-8 x 10(10) particle units (pu), n = 2/group) into the lung airway epithelium of six normal individuals. Serum, ELF, and endobronchial biopsies were obtained at baseline and at various time points following vector administration. In contrast to the observations in experimental animals in which lung administration of first-generation Ad vectors is followed by strong systemic and local host response, bronchial spray administration of the Ad vector to normal humans showed: (1) minimal inflammation in bronchial biopsies, bronchial brushing, and bronchoalveolar lavage fluid; (2) no blood lymphocyte proliferation in five of six individuals in response to in vitro stimulation with Ad antigens; and (3) no significant increase from baseline in blood or lung ELF anti-Ad neutralizing antibodies. Despite this minimal normal human anti-Ad host response, dose-dependent levels of vector DNA in the airway epithelium were transient. Vector DNA in the targeted airway epithelial cells peaked in a dose-dependent fashion at 0.007 to 1.1 copies/cell at day 7 and declined thereafter, reducing to <10% of peak levels by 2 weeks. These observations demonstrate both the strengths and the limits of using experimental animals to predict human responses to gene transfer vectors. While the transient nature of Ad vector persistence in the airway epithelium is predicted by most experimental animal studies, respiratory epithelial administration of first-generation Ad vectors at doses up to 10(10) pu to airway epithelium of healthy individuals elicits minimal to no detectable systemic and mucosal humoral and cellular immune responses, an observation diametrically opposed to the host responses measured in experimental animals. These findings suggest that, while adaptive anti-Ad immune responses likely play some role in the disappearance of the vector DNA following vector administration to the human lung, other mechanisms may also be involved in the response of humans to Ad gene transfer vectors.

Adenoviridae↗

PubMed1996

Symptomatic urinary tract infection in women in primary health care. Bacteriological, clinical and diagnostic aspects in relation to host response to infection.

OBJECTIVE: To evaluate rapid diagnostic tests for bacteriuria in women with symptoms of urinary tract infection (UTI), and to analyse bacteriological and clinical findings in relation to host response to infection. DESIGN: Prospective study of symptomatic UTI in women. SETTING: Primary health care centres. PATIENTS: 819 women with signs and symptoms suggestive of UTI. MAIN OUTCOME MEASURES: History of UTI and clinical findings were recorded. After randomization but before antibiotic treatment, urine specimens were analysed for pyuria by sediment microscopy and for nitrite using a test strip, and cultures were performed. The systemic inflammatory response was assessed by C-reactive protein (CRP), erythrocyte sedimentation rate, and total white blood cell count. RESULTS: The combined use of tests for pyuria and nitrite resulted in a high sensitivity (0.93) and efficacy (0.85) when the prevalence of bacteriuria was 0.89. Escherichia coli and Staphylococcus saprophyticus accounted for 93% of the urinary isolates. Significantly more patients infected with S. saprophyticus than E. coli complained of dysuria (p < 0.05), frequency (p < 0.05) or flank pain (p < 0.01). CRP agreed best with the clinical diagnosis of acute pyelonephritis. CONCLUSIONS: In women with a high probability of bacteriuria, i.e. those with symptoms of lower UTI, examination for pyuria and urinary nitrite offers high diagnostic efficacy. If either or both tests are positive urine cultures can be omitted.

Adolescent↗

PubMed1995

The effect of cyclosporin A, FK506, and rapamycin on the murine chronic graft-versus-host response--an in vivo model of Th2-like activity.

We have evaluated the effects of three potent immunosuppressive agents: cyclosporin A, FK506, and rapamycin, on a murine chronic graft-versus-host response (chronic GVHR). The chronic GVHR has previously been described to be a Th2-like response, and is characterized by a marked splenomegaly and hyper-IgE production in the early stages of the response. The effects of the immunosuppressive agents on both splenomegaly and hyper-IgE were measured 3 weeks after the induction of the chronic GVHR. Rapamycin was found to inhibit both splenomegaly and the hyper-IgE response in a dose-dependent manner. Unexpectedly cyclosporin A and FK506 were found to potentiate markedly both the splenomegaly and hyper-IgE response at low doses before exhibiting an inhibitory effect at higher doses. We propose the differences of activity seen with rapamycin compared with cyclosporin A and FK506 may be explained by their different mechanisms of action, and also by the selectivity of low dose cyclosporin A and FK506 for Th1-like lymphocytes. The implications of these observations are discussed in relation to the use of these immunosuppressives for the treatment of Th2-like diseases.

Animals↗

PubMed2001

Host response to infection: the role of CpG DNA in induction of cyclooxygenase 2 and nitric oxide synthase 2 in murine macrophages.

Depending on sequence, bacterial and synthetic DNAs can activate the host immune system and influence the host response to infection. The purpose of this study was to determine the abilities of various phosphorothioate oligonucleotides with cytosine-guanosine-containing motifs (CpG DNA) to activate macrophages to produce nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and to induce expression of NO synthase 2 (NOS2) and cyclooxygenase 2 (COX2). As little as 0.3 microg of CpG DNA/ml increased NO and PGE(2) production in a dose- and time-dependent fashion in cells of the mouse macrophage cell line J774. NO and PGE(2) production was noted by 4 to 8 h after initiation of cultures with the CpG DNA, with the kinetics of NO production induced by CpG DNA being comparable to that induced by a combination of lipopolysaccharide and gamma interferon. CpG DNA-treated J774 cells showed enhanced expression of NOS2 and COX2 proteins as determined by immunoblotting, with the relative potencies of the CpG DNAs generally corresponding to those noted for the induction of NO and PGE(2) production as well as to those noted for the induction of interleukin-6 (IL-6), IL-12, and tumor necrosis factor. Extracts from CpG DNA-treated cells converted L-arginine to L-citrulline, but the NOS inhibitor N(G)-monomethyl-L-arginine (NMMA) inhibited this reaction. The COX2-specific inhibitor NS398 inhibited CpG DNA-induced PGE(2) production and inhibited NO production to various degrees. The NOS inhibitors NMMA, 1400W, and N-iminoethyl-L-lysine effectively blocked NO production and increased the production of PGE(2) in a dose-dependent fashion. Thus, analogues of microbial DNA (i.e., CpG DNA) activate mouse macrophage lineage cells for the expression of NOS2 and COX2, with the production of NO and that of PGE(2) occurring in an interdependent manner.

Adjuvants, Immunologic↗

PubMed1963

MODIFICATION OF HOST RESPONSES TO BACTERIAL ENDOTOXINS. I. SPECIFICITY OF PYROGENIC TOLERANCE AND THE ROLE OF HYPERSENSITIVITY IN PYROGENICITY, LETHALITY, AND SKIN REACTIVITY.

Evidence is presented suggesting that the apparent non-specificity of pyrogenic tolerance observed with Gram-negative bacterial endotoxins is due to related antigenic determinants associated with the macromolecular toxins. This is based on results obtained in rabbits from pyrogenic cross-tolerance tests with selected endotoxins. In these tests, purified endotoxins from Escherichia coli (COO8) and Chromobacterium violaceum (CV) gave results one might expect with non-reciprocal cross-reacting antigens in classical immune systems. Additional evidence for an immune mechanism in tolerance is suggested by the highly significant anamnestic response observed. Lipid A, a toxic derivative of the purified COO8 endotoxin, failed to induce pyrogenic tolerance against the parent toxin. These results are explained by assuming that endotoxins have two interdependent activities associated with different portions of the macromolecule; one is assumed to be responsible for the primary toxicity, and the other is involved in secondary toxicity. The latter is dependent on the hypersensitive state of the host. Additional evidence for the role of hypersensitivity in secondary toxicity is based on the observation that adult rabbits are highly sensitive to the pyrogenic, lethal, and skin-reacting activities of endotoxin in contrast to young animals which are more resistant to all of these attributes of toxicity. In adults, the host responses to pyrogenicity, lethality, and skin reactivity could be partially inhibited by the early exposure of the animals to massive doses of endotoxin equivalent to a LD(50). The pyrogenic tolerance shown in these animals was specific indicating that the inhibition of the hypersusceptibility to endotoxin involved an immunological mechanism. A mechanism of endotoxin tolerance is proposed and discussed based on the induction of specific antibodies capable of assisting the RES in the clearance and destruction of endotoxin. It is suggested that the present inconsistencies relative to the chemical nature and biological activities of endotoxins might be explained on the basis of these two activities and the failure to recognize the importance of the immunological state of the host in which the toxins are tested.

Animals↗

PubMed2006

Pivotal Advance: eosinophil infiltration of solid tumors is an early and persistent inflammatory host response.

Tumor-associated eosinophilia has been observed in numerous human cancers and several tumor models in animals; however, the details surrounding this eosinophilia remain largely undefined and anecdotal. We used a B16-F10 melanoma cell injection model to demonstrate that eosinophil infiltration of tumors occurred from the earliest palpable stages with significant accumulations only in the necrotic and capsule regions. Furthermore, the presence of diffuse extracellular matrix staining for eosinophil major basic protein was restricted to the necrotic areas of tumors, indicating that eosinophil degranulation was limited to this region. Antibody-mediated depletion of CD4+ T cells and adoptive transfer of eosinophils suggested, respectively, that the accumulation of eosinophils is not associated with T helper cell type 2-dependent immune responses and that recruitment is a dynamic, ongoing process, occurring throughout tumor growth. Ex vivo migration studies have identified what appears to be a novel chemotactic factor(s) released by stressed/dying melanoma cells, suggesting that the accumulation of eosinophils in tumors occurs, in part, through a unique mechanism dependent on a signal(s) released from areas of necrosis. Collectively, these studies demonstrate that the infiltration of tumors by eosinophils is an early and persistent response that is spatial-restricted. It is more important that these data also show that the mechanism(s) that elicit this host response occur, independent of immune surveillance, suggesting that eosinophils are part of an early inflammatory reaction at the site of tumorigenesis.

Animals↗

PubMed2002

Nods: a family of cytosolic proteins that regulate the host response to pathogens.

Genetic variation in Nod2 is associated with susceptibility to Crohn's disease. Nod2 and its homologue, Nod1, are members of a growing family of cytosolic factors related to the apoptosis regulator Apaf-1 and a class of plant disease resistance proteins. Nod1 and Nod2 confer responsiveness to lipopolysaccharides and interact with RICK, a mediator of NF-kappaB activation. Nod1 and Nod2 and related Nods appear to regulate the host response to pathogens, a process that may be faulty in certain inflammatory diseases. Recent studies that suggest that Nods may be involved in the recognition of pathogen components in the cytosol of mammalian cells are reviewed.

Adaptor Proteins, Signal Transducing↗

PubMed1996

Use of a new glass microfibre histamine release method to study the modulation of the host response in human schistosomiasis mansoni. Individuals with different degrees of exposure to the disease show differing antibody biological function.

A new glass microfibre histamine release method was used to study the modulation of the host response in human schistosomiasis mansoni to improve our understanding of the role of basophils in the development of immunity in schistosomiasis mansoni. The histamine release from umbilical cord blood basophils sensitized with sera from Sudanese individuals infected with Schistosoma mansoni was measured. Schistosomiasis sera (n = 113) were able to passively sensitize basophils and induce a positive histamine release in response to whole worm homogenate (WWH) (chi 2 = 40.5, P < 0.0001) and soluble egg antigen (SEA) (chi 2 = 16.3, P < 0.0001). However, worm antigen induced significantly higher histamine release in adults than egg antigen (Z = 4.83, P < 0.0001). Basophil cell sensitivity to WWH was inversely related to the intensity of infection. A correlation was observed between basophil cell sensitivity and IgE antibodies in response to WWH. Chronically infected canal cleaners (n = 16) showed a significant increase in basophil cell sensitivity 3 months after praziquantel treatment (Z = 1.73, P < 0.05). Normally exposed adults (n = 29) showed a significant decrease in basophil cell sensitivity 1 year after treatment. When serum fractions were used, chronically infected canal cleaners showed a significant increase in histamine release after IgG removal (P < 0.05) Comparison between the different study groups with regard to resistance and susceptibility to reinfection, their basophil sensitizing ability and antibody response showed a difference in the biological function of the IgE to WWH in the different groups. Direct histamine release results from S. mansoni infected individuals from outside the endemic area (Danish) showed the possibility of using the glass microfibre histamine release method in the diagnosis of schistosomiasis.

Adult↗

PubMed1994

Host responses in patients with generalized refractory periodontitis.

Although patients with refractory periodontitis have been widely reported, no clear biologic profile of these patients has been noted. The purpose of the present study was to evaluate host responsiveness of a well-defined group of refractory periodontitis patients by determining the effect of a lipopolysaccharide (LPS) challenge on monocyte surface receptor density and on the release of inflammatory mediators. Venous blood was obtained from 7 refractory periodontitis, 8 stable periodontal maintenance, and 8 gingivitis patients with no evidence of periodontitis. Mononuclear cells were cultured in either control media or media treated with Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), or Salmonella typhimurium (S. typh) LPS. At 0 and 24 hours supernatants were assayed for prostaglandin-E2 (PGE2) and interleukin-1 beta (Il-1 beta) release by ELISA. Using flow cytometry the density of specific monocyte surface receptors were assayed with Mo3e and LeuM3 monoclonal antibodies (mAb); T-cell CD4/CD8 ratios were assayed with OKT-3, OKT-4, and OKT-8 mAb. After 24 hours incubation with Pg or S. typh LPS, the upregulation of the Mo3e receptor was significantly decreased for refractory periodontitis patients (P < 0.05) when compared to gingivitis and to stable maintenance patients. In refractory periodontitis patients the T-cell CD4/CD8 ratio was decreased. Upon stimulation with Pg or S. typh LPS, monocytes from stable maintenance and refractory periodontitis patients released more Il-1 beta (P < 0.05) and PGE2 (P = 0.13 and 0.15) than monocytes from gingivitis subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

The effect of elevated levels of thromboxane on host response to tumor.

Previous studies have demonstrated that human malignancies can synthesize large amounts of thromboxane. It has also been reported that thromboxane can significantly alter multiple components of physiologic and immunologic function. We investigated the effect of elevated levels of thromboxane on host response to tumor using multiple rat models, and the long acting thromboxane analogue U-46619. Administration of the thromboxane analogue was not found to significantly alter the growth of primary tumors or peritoneal metastases. The analogue was found to significantly decrease mean survival time with a pulmonary metastases model. The thromboxane analogue failed to alter macrophage cytotoxicity, lymphocyte cytotoxicity, T lymphocyte subset numbers, or lymphocyte blastogenic response. Administration of the thromboxane analogue decreased the rate of lymphocyte metabolism of glucose and decreased lymphocyte intracellular adenosine deaminase activity. In conclusion, elevated thromboxane levels do not appear to alter primary tumor growth or host immune function, but do decrease resistance to pulmonary metastases.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1992

Effects of biostability and morphology on host response of polyurethane-based soft tissue implants.

Polyurethane has been found to be one of the most successful polymers for soft tissue applications. We have investigated the effect of material biostability and morphology on the host response of polyurethane-based soft tissue implants in rabbits. The polyurethane containing allophanate linkage was prepared by using hexamethylene diisocyanate, polypropylene glycol (400) and 1,4-butane diol. Biuret-based biostable polyurethanes were prepared by using hexamethylene diisocyanate, polytetramethylene glycol and trimethylol propane and water. Samples of circular button and rectangular specimens were implanted subcutaneously in rabbits in the paravertebral region for a post-implantation period of 9 months. Relatively larger polyurethane samples with different morphology elicit a varied tissue response with our candidate polyurethane materials. A favorable tissue response was observed with rectangularly shaped thin polyurethane. Giant cell reaction, absence of fibrous tissue encapsulation and degradation were noticed for the rectangular smooth samples at the end of post-implantation period of 9 months. No malignant changes were noticed in any of these samples.

Animals↗

PubMed2004

Investigations on four host response factors whose expression is enhanced in X4 SHIV encephalitis.

HIV encephalopathy, one of the major complications of HIV infection, involves productive virus replication in macrophages in the brain in association with heightened expression of several host response factors. One or more of these factors are thought to be the cause of the degenerative changes in neurons in the brain. Macaques infected with SIV and SHIV viruses have provided excellent working models for studying mechanisms of the human disease. Although HIV encephalopathy is primarily associated with CCR5-utilizing viruses, our findings have shown that CXCR4-utilizing SHIVs were also capable of causing the syndrome in rhesus macaques. In SHIV-infected macaques, approximately 30% of the animals developed encephalitis. In order to understand the factors leading to end-stage encephalitis, we performed microarray analyses on brains of encephalitic and non-encephalitic-infected macaques, and found pronounced enhancement of expression of interleukin-4, platelet-derived growth factor-B chain, monocyte chemoattractant protein-1 and CXCL10 in the brains of the encephalitic animals. This review discusses the role of each of these factors in mediating SHIV encephalitis.

Animals↗

PubMed2002

Modulation of the host response in periodontal therapy.

This paper was prepared by the Research, Science, and Therapy Committee of the American Academy of Periodontology to provide the dental profession an overview of current and potential methods to modulate the host response in the treatment of periodontal diseases. Specifically, it discusses components of periodontal disease pathogenesis (i.e., immune and inflammatory responses, excessive production of matrix metalloproteinases and arachidonic acid metabolites, and regulation of bone metabolism) and their modulation.

Alveolar Process↗