Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Immune toxicities”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1977

Relationship between Escherichia coli endotoxin toxicity and the immunization status of normal adult guinea-pigs.

Lipopolysaccharide extracts of E. coli (endotoxins) were toxic to normal adult guinea-pigs, yet no evidence was found of serological reactivity to endotoxins or of "immediate" dermal reactivity in vivo. In contrast, testing of the serum of experimentally immunized animals provided evidence of precipitins, agglutinins and haemolysins. It is concluded that endotoxin exerts toxic effects in the absence of significant antibody production. This suggests that endotoxin toxicity is independent of immune processes not involving cell-mediated responses.

Animals↗
PubMed1978

[Effect of thiamine on the formation of immune response in toxic lesions of the liver].

The authors studied the influence of various doses of thiamine on the formation of immune response in the animals with toxic affection of the liver. As revealed, thiamine in a dose of 400 microgram per kg of body weight inhibited the formation of the immune response in healthy rats, but failed to influence this process in the animals with toxic affection of the liver. Thiamine in a dose of 100 microgram per 100 g of body weight stimulated the formation of the immune response in healthy rats and in those poisoned with carbon tetrachloride. The simulating effect of thiamine was more pronounced in poisoned than in healthy rats. The blood serum of rats poisoned with carbon tetrachloride enhanced the immunostimulating action of thiamine.

Animals↗
PubMed1977

Neutralization of heterologous toxicities in mice immunized with proteins from S. typhimurium and from a human pathogen (S. emek).

Groups of mice immunized with proteins from S. typhimurium and from a non-pathogenic Salmonella for mice (S. emek) were infected with S. tymphimurium, S. emek, S. blockley and S. paratyphi A. The mice immunized with the S. typhimurium proteins were, as always protected against infection with the pathogen and resisted the toxicities, which killed the controls, of S. paratyphi A and S. emek but not of S. blockley. The mice immunized with S. emek proteins resisted the toxicity of S. paratyphi A and, to a lesser degree, that of the homologous S. emek. The animals did not resist the toxicity of a similar concentration of S. blockley and the immunized mice died, like the controls, within 20-40 hours. Mice in this group infected with S. typhimurium had a much longer delay before dying, than the controls. Antiprotein antibodies present in the sera of the immunized mice are, apparently, responsible for the neutralization of the toxicities of the heterologous strains and for the eventual protection against infection.

Animals↗
PubMed1979

Experimental and clinical studies on toxicity of xenogeneic tumor-specific immune ribonucleic acid.

To learn the toxicity of xenogeneic tumor-specific immune ribonucleic acid (I-RNA), experimental and clinical studies were carried out. Experimentally, doses of 30 mg/kg, 15 mg/kg, 7.5 mg/kg or 3.75 mg/kg of xenogeneic I-RNA extracted from lymphoid tissues of rabbits sensitized with 105,000 Xg sediments of human gastric carcinoma tissue were injected intraperitoneally into Wistar rats once a day for 30 days. During the period of the study, changes of physiological and biochemical values were examined. In addition, pathological study was made for each organ after the I-RNA administration. There was no death during the study. In the groups of high dose administration, there were poor increase in the body weight, elevation of GOT, GPT and LDH, findings of vacuolar degeneration of hepatic cells, and increase of mesangial matrix and polynuclear glomerulus. Throughout the experiment, the groups given 7.5 mg/kg and 3.75 mg/kg of I-RNA showed no significant difference from control groups. Clinically, 31 cases treated with passive immunotherapy with allogeneic lymphocytes, preincubated with xenogeneic I-RNA, were examined retrospectively for the difference in hematological and biochemical data before and after the therapy. One case showed a transient mild febrile reaction after the therapy. There was no significant difference in hematological and biochemical data. Pathological findings in 3 autopsies after the treatment were reported.

Adult↗
PubMed2025

Genetic haplotypes in VWA8, OSBPL6, and ADAMTS9-AS2 are associated with immune-related adverse effects in ICI-treated patients with cancer.

BACKGROUND: Immune-related adverse events (irAEs) remain largely unpredictable, potentially affecting multiple organ systems and occurring at almost any point during and even occasionally after immune checkpoint inhibitor (ICI) treatment. To identify populations at risk for these immune-mediated toxicities, we analyzed genetic characteristics and immune markers associated with clinically significant irAEs. METHODS: We carried out a genome-wide association study on 373 white patients receiving ICI treatment. We identified single nucleotide polymorphisms associated with irAEs. Blood cytokine profiling and peripheral blood mononuclear cell RNA sequencing were performed at pretreatment baseline and 6-8 weeks after ICI initiation. Findings were validated in two external cohorts. RESULTS: We identified genetic haplotypes in VWA8 (Von Willebrand Factor A Domain Containing 8), OSBPL6 (Oxysterol Binding Protein Like 6), and ADAMTS9-AS2 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif 9 Antisense RNA 2) associated with grade &#x2265;2 irAEs. Patients carrying risk haplotypes for one or more genes exhibited significantly greater rates of grade &#x2265;2 (OR 3.02; 95%&#x2009;CI 1.83 to 5.02; p<0.001), grade &#x2265;3 (OR 3.59; 95%&#x2009;CI 1.93 to 6.64; p<0.001), and multiple type irAE (OR 2.60; 95%&#x2009;CI 1.53 to 4.39; p<0.001). Serum CCL3 levels were significantly elevated in individuals carrying risk haplotypes (p=0.03). Gene expression analysis demonstrated activated autoimmune and inflammatory pathways in the genetic risk group. CONCLUSIONS: Novel polymorphisms in VWA8, OSBPL6, and ADAMTS9-AS2 may impact immune pathways, promote inflammation, potentiate autoimmune phenotypes, and convey risk of irAE in ICI-treated patients.

Humans↗
PubMed1976

Canine allogeneic bone marrow transplantation. Technique and variables influencing engraftment.

We have studied the toxicity and immune suppression of supralethal total body irradiation (800-2000 rads, 60Co) at three dose intensities (10 rads/min, 49 rads/min, and 100 rads/min). In 79 intensively supported radiation control animals, the LD50(5) (tn 5 days) for these dose intensities is estimated to be 1556, 941, and 921 rads, respectively. A biomodal pattern of early (median 4 days) and late (median 9 days) deaths was observed corresponding to histopathological evidence of the intestinal and hematopoietic radiation syndromes. Random donor bone marrow transplants were performed in 83 animals to test immune suppression afforded by 800 rads and 1000 rads at dose intensities of either 10 rads/min or 49 rads/min. Bone marrow cell dose was varied to analyze its effect on engraftment. A greater degree of immunosuppression with less toxicity was achieved at the lower dose intensity. A minimum dose of 3-5 X 10(8) nucleated allogeneic bone marrow cells/kg (readily obtainable from living donors) resulted in a high percentage of engraftment with lethal graft-versus-host disease following conditioning with 1,000 rads midplane at 10 rads/min, the optimum regimen employed.

Animals↗
PubMed2026

Environmental benzene exposure induces a conserved neutrophil degranulation program across species.

Immune systems have evolved under constant pressure from pathogens and environmental challenges, leading to the emergence of conserved defense mechanisms across diverse organisms. Evidence indicates that environmental exposures perturb immune regulatory networks, particularly during development, when transcriptional programs governing hematopoiesis, immune cell differentiation, and inflammatory signaling are highly dynamic and sensitive to external stressors. Volatile organic compounds represent an important but incompletely understood source of immunological perturbation. Among these, benzene is a ubiquitous environmental contaminant associated with hematotoxicity and immune dysregulation; however, transcriptional responses to environmentally relevant low-level exposures during development remain poorly characterized. To determine whether benzene exposure engages conserved cross-species immune regulatory pathways, we performed a comparative transcriptomic analysis integrating developmental tissues from 3 vertebrate systems: human placenta, murine placenta, and zebrafish larvae. Bulk RNA sequencing datasets were analyzed to identify transcriptional responses associated with benzene exposure in experimental models (&#x2264;5&#x2009;ppm) and with benzene adduct levels in maternal plasma for human samples. Because placental gene expression exhibits strong sexual dimorphism, murine datasets were stratified by fetal sex. Pathway- and network-level analyses were used to identify conserved biological responses. We observed a striking convergence on activation of innate immune pathways associated with neutrophil degranulation, IL-8 signaling, and Rho GTPase-mediated inflammatory responses. Further, network analyses identified CXCL8 and ERK1/2 as shared regulatory hubs linking transcriptional responses across datasets. Together, these findings uncover an evolutionarily conserved innate immune signature associated with benzene exposure during vertebrate development, suggesting that environmental chemical perturbations may disrupt fundamental immune regulatory programs across species.

Animals↗
PubMed2022

Battle for Metals: Regulatory RNAs at the Front Line.

Metal such as iron, zinc, manganese, and nickel are essential elements for bacteria. These nutrients are required in crucial structural and catalytic roles in biological processes, including precursor biosynthesis, DNA replication, transcription, respiration, and oxidative stress responses. While essential, in excess these nutrients can also be toxic. The immune system leverages both of these facets, to limit bacterial proliferation and combat invaders. Metal binding immune proteins reduce the bioavailability of metals at the infection sites starving intruders, while immune cells intoxicate pathogens by providing metals in excess leading to enzyme mismetallation and/or reactive oxygen species generation. In this dynamic metal environment, maintaining metal homeostasis is a critical process that must be precisely coordinated. To achieve this, bacteria utilize diverse metal uptake and efflux systems controlled by metalloregulatory proteins. Recently, small regulatory RNAs (sRNAs) have been revealed to be critical post-transcriptional regulators, working in conjunction with transcription factors to promote rapid adaptation and to fine-tune bacterial adaptation to metal abundance. In this mini review, we discuss the expanding role for sRNAs in iron homeostasis, but also in orchestrating adaptation to the availability of other metals like manganese and nickel. Furthermore, we describe the sRNA-mediated interdependency between metal homeostasis and oxidative stress responses, and how regulatory networks controlled by sRNAs contribute to survival and virulence.

Bacteria↗
PubMed1978

Modification of hepatotoxic effects of aflatoxin B1 in rabbits by immunization.

Reduction of acute toxic effect of aflatoxin B1 was achieved by immunizing the rabbits with small amounts of bovine serum albumin-aflatoxin B1 conjugate. Rabbits after immunization showed lower mortality, near normal serum isocitric dehydrogenase activity, no abnormality in livers when challenged with a single dose of aflatoxin B1. The results suggest that immunization might be used prophylactically against aflatoxicosis.

Aflatoxins↗
PubMed1979

Matching of chemotherapy to mouse strain and lymphoid tumor type to prevent tumor-induced suppression of specific T- and B-cell functions.

Specific immunological and hematopoietic functions were studied during treatment with antineoplastic agents in mice bearing syngeneic lymphoid tumors: 70Z/2, a B-cell lymphoma of C57BL X DBA/2 F1 (hereafter called (BD2F1) mice; EL4, a T-cell lymphoma of C57BL/6 mice; or J774, a macrophage tumor of BALB/c mice. Both B- and T-lymphocyte function (antibody-forming cells and cell-mediated lymphocyte lympholysis toward alloantigens) were suppressed in spleen cells of mice bearing these tumors. Other hematopoietic functions (granulocyte, macrophage, and megakaryocyte progenitor cells) were variably influenced by growth of these lymphoid tumors. J774 enhanced, but 70Z/2 suppressed, megakaryocyte progenitor cells. J774 and 70Z/2 increased levels of granulocyte-macrophage progenitor cells. EL4, the T-cell lymphoma, did not influence either cell type. Significant variation in strain sensitivity to drug toxicity and drug effectiveness in different tumor-host systems was observed. Increased median survival time with reversal of tumor-induced immune dysfunction, without toxicity to hematopoietic progenitor cells, was realized in two tumor-host-drug combinations. Polyinosinic-polycytidylic acid was effective against J774, while actinomycin D was active against 70Z/2. Mitomycin C effectively reduced tumor load, as evidenced by loss of splenic tumor colony-forming cells for all three tumors. This agent prolonged survival and concomitantly restored immunological responsiveness in hosts immunosuppressed by growth of 70Z/2 or J774. Paralleling tumor reduction with mitomycin C therapy, the splenic hematopoietic progenitor and colony-forming B-cells were reduced in tumor-bearing and tumor-free mice, thus compromising its therapeutic effectiveness. 1-beta-D-Arabinofuranosylcytosine reduced tumor load with marginal toxicity toward hematopoietic progenitor and colony-forming B-cells. However, immune responsiveness was only partially restored, and median survival was not increased. The results presented show the diversity of therapeutic drug effectiveness in increasing mean survival time and influencing other life-sustaining parameters (immunological and hematopoietic functions).

Animals↗
PubMed1978

Melanoma specific protein: occurrence in the urine of patients with halo naevus and vitiligo.

Melanoma specific protein is immunologically related to altered naevus cell cytoplasm. It is excreted by patients with malignant melanoma but in no other malignancy. The protein has been detected in patients with actively developing halo naevi but not when repigmentation is taking place. It also occurs in patients with very active vitiligo but in no other pigment condition we have studied. It is suggested that the protein is a marker of active destruction of naevus cells by immune mechanisms and that the release of toxic materials during this immune reaction may be responsible for the production of the halo phenomenon and for the areas of vitiligo that may be seen elsewhere on the skin.

Adolescent↗
PubMed1975

[Toxicological characteristics of ampicillin].

Toxocity of ampicillin trihydrate was studied in acute and chronic experiments. It was shown that the antibiotic had low acute toxicity, did not cumulate and had no skin-irritating effect. On its inhalation in concentrations of 5 mg/m3 for 4 months, ampicillin induced allergization of albino rats, decreased their immunity. The general toxic effect of the drug was slightly pronounced. Ampicillin in a concentration of 0.1 mg/m3 induced tension of the immunological reactivity of the organism. The maximum permissible concentration (MPC) of ampicillin in the working premises equal to 0.1 mg/m3 is recommended. Mark "Allergen" is necessary.

Ampicillin↗
PubMed1979

Methods to evaluate the effects of toxic materials deposited in the lung on immunity in lung-associated lymph nodes.

Intratracheal instillation of sheep red blood cells (SRBC) induced a primary immune response in lung-associated lymph nodes of Chinese hamsters and Fischer-344 rats. Few or no anti-SRBC antibody forming cells (AFC) were found in the spleen or cervical lymph nodes after intratracheal immunization. The number of AFC was significantly suppressed in the lung-associated lymph nodes from hamsters exposed by inhalation of 239PuO2 and in rats exposed by intratracheal instillation of benzo(a)pyrene (BaP). Although the immunologic function of the lung-associated lymph nodes was suppressed by 239PuO2 and BaP exposure, there was no observable increase in the number of AFC in distant lymphoid tissues. These data indicate that damage to lung cells and/or cells in lung-associated lymph nodes can suppress immunity induced by deposition of antigen in the lung. Even though lung-associated lymph nodes in exposed animals contained lower numbers of AFC, antigen instilled into the lungs of exposed animals did not significatnly translocate to distant lymphoid tissues. This indicates that the antigen filtering capacity of the lung-associated lymph nodes was not altered.

Aerosols↗
PubMed1979

[Suppression of humoral antibody synthesis on exposure to hyperbaric oxygenation].

The influence of hyperbaric oxygenation (HBO) on the immune response in mice, immunized intraperitoneally with sheep red blood cells, was studied. HBO was shown to reduce hemagglutinin and hemolysin titres in peripheral blood as well as to decrease the amount of antibody-forming cells in the spleen. The most pronounced immunodepressant HBO effect is seen when hyperbaric oxygenation is carried out under toxic conditions before immunization of the animals with low antigen doses. Relationship is shown between the immunodepressant HBO effect and reduced leucocyte and lymphocyte counts in peripheral blood of the animals.

Animals↗
PubMed2026

Safety, humoral and cellular immune responses to a pre-pandemic adjuvanted influenza A (H5N8) vaccine.

Highly pathogenic avian influenza (HPAI) A(H5) viruses can be transmitted from infected birds to various mammalian species, including humans. Avian influenza viruses (AIVs), members of the Orthomyxoviridae family, possess segmented RNA genomes prone to reassortment, favoring the emergence of novel genetic traits that may alter transmissibility, pathogenicity, and antigenicity. Although no sustained human-to-human transmission has been reported, the potential adaptation of these viruses poses a significant pandemic threat. This study aimed to evaluate the non-clinical safety, toxicity, and humoral immune responses induced by an adjuvanted H5 influenza vaccine in rats and rabbits, to support future clinical safety trials in humans. Male and female Wistar rats and New Zealand rabbits were observed for 14, 28, and 90&#xa0;days after receiving two intramuscular doses of the H5N8 vaccine (15&#xa0;&#x3bc;g HA/dose) formulated with the IB160 oil-in-water emulsion adjuvant. No systemic comorbidities, central nervous system alterations, or relevant clinical signs were observed. Hematological parameters remained within normal ranges, with total and differential leukocyte counts showing only minor fluctuations (<1% of total leukocytes). Mild biochemical variations in urea and hepatic transaminase levels were not correlated with histopathological alterations. The vaccine elicited a robust humoral response soon after immunization, with all groups reaching protective HAI-antibody titers. Although antibody levels declined over time, particularly in males, they remained significantly above baseline, indicating durable immunological memory. Furthermore, the vaccine induced a specific cellular immune response, confirmed by IL-2 and TNF production by antigen-specific T lymphocytes in splenic cell cultures after the booster dose. In conclusion, the H5N8 vaccine with the IB160 adjuvant was well tolerated locally and systemically, without compromising vital organ function. The safety and immunogenicity findings are consistent with expectations for adjuvanted influenza vaccines, demonstrating strong and durable humoral and cellular immune responses.

H5N8 influenza vaccine↗
PubMed1978

Antibody-linked cytotoxic agents in the treatment of cancer: current status and future prospects.

Antibodies against tumor cell surface antigens have been used as selective carriers of anticancer drugs, which themselves lack selectivity. Although such antibodies have been demonstrated in tumor hosts, xenogeneic antitumor sera should provide larger yields of better-defined antitumor antibodies for therapeutic purposes. This review examined factors that influence the immune response to tumor-associated transplantation antigens (TATA) and the methods for rendering tumor cells more immunogenic. Consideration was also given to techniques for elimination of irrelevant immunoglobulin molecules. These could involve purification of both antitumor sera and TATA fractions for immunization, as well as tailoring of the immunization protocol. Various toxic agents that have been linked to antitumor globulins with retention of agent and antibody activity were tabulated: alkylating drugs, antibiotics, antimetabolites, cell surface agents, protein synthesis inhibitors, and unconventional anticancer agents that selectively convert nontoxic arsenicals or halides into cytocidal derivatives. The methods by which effective conjugates can be produced and their possible mode of action were described for the different types of agents. Several problems inherent in this modality of tumor therapy include: 1) the necessity of binding therapeutically effective amounts of antitumor agent, 2) ensuring of delivery of drug in active form to target sites, 3) avoidance of host reactions to foreign proteins, and 4) possible emergence of resistant tumor cell populations. Antibody-linked cytotoxic agents may find their greatest use in the eradication of small numbers of circulating tumor cells and micrometastases remaining after removal of primary tumors.

Alkylating Agents↗
PubMedDate not supplied

New bioassay for screening immunotoxic agents.

A new bioassay for evaluation of compounds potentially toxic for the immune system is described. It is suitable for the measurement of enhancement of primary antibody response and of enhancement and inhibition of memory development in vivo. It utilizes immunoenzymatic techniques which can readily be automated and thus allow the screening of many compounds at relatively low cost. It can provide answers regarding the safety or danger of each compound tested within 30-45 days.

Animals↗