SEARCH · PubMed Health

Results for “Toxic inflammation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original 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

PubMed2025

Immune dysfunction in Alzheimer disease.

Emerging evidence highlights the crucial role of peripheral immune cells in maintaining brain homeostasis and their influence on the pathology of Alzheimer disease (AD). Genome-wide association studies have identified numerous AD risk variants in genes expressed by immune cells, implicating innate and adaptive immune pathways in disease progression. Advances in neuroimmunology have revealed that immune cell crosstalk involving T cells, B cells, monocytes and/or macrophages and neutrophils can modulate the hallmark features of AD, including amyloid plaque accumulation, tau pathology and chronic neuroinflammation. Mechanistic insights suggest that chronic peripheral inflammation, immune exhaustion, metabolic dysfunction and epigenetic reprogramming exacerbate neurodegeneration in AD by promoting toxic inflammation and impairing protein clearance in the brain. These findings may catalyse the development of novel immunomodulatory strategies, such as immune checkpoint inhibition and cytokine targeting, among others, for AD. This Review examines peripheral immune alterations in AD, evaluates related therapeutic opportunities and highlights key knowledge gaps, particularly the need for human-derived data to advance translational progress. Future research should prioritize personalized approaches that integrate genetic risk, immune profiling and ageing to inform next-generation therapies for AD.

Humans↗

PubMed2026

Establishment of a STAT6 Reporter Assay for Screening Environmental Toxicants Affecting Allergic Airway Inflammation.

Air pollution-associated allergic airway inflammation is an increasing public health concern. Interleukin‑4 (IL‑4) and interleukin‑13 (IL‑13), which activate the Signal Transducer and Activator of Transcription 6 (STAT6) pathway, a central mediator of allergic airway inflammation, may modulate the respiratory toxicities of pollutants. The present study describes the generation and validation of a stable STAT6 luciferase reporter assay in human airway epithelial cells for evaluating environmental toxicants that modulate STAT6 signaling. Human bronchial epithelial 16HBE14o- cells were transduced with a STAT6-responsive luciferase reporter using a lentiviral vector, followed by optimization of puromycin selection and multiplicity of infection, and monoclonal isolation by limiting dilution. A stable clone with strong and reproducible induction across serial passages was selected. Reporter responsiveness was validated by IL-4/IL-13 stimulation, and STAT6 dependence was confirmed using selective STAT6, STAT5, and STAT3 inhibitors. Assay performance was quantified by Z'-factor analysis, which indicated reproducible signal separation. Furthermore, the assay was applied to individual air-pollution constituents, and benzo[b]fluoranthene and particulate matter significantly increased STAT6 reporter activity. This method provides a scalable approach for measuring STAT6 activity in airway epithelial cells and for prioritizing environmental toxicants that modulate allergic airway signaling.

STAT6 Transcription Factor↗

PubMed2026

Integrative multi-omics analysis reveals lipid/metabolite dysregulation and temporal decoupling in disease progression.

Our study presents and applies a metabolomics-driven multi-omics integration strategy to elucidate dynamic pathway interactions during disease progression. We analyzed longitudinal metabolomics datasets from a Duchenne muscular dystrophy (DMD) mouse model (6-30 weeks) and an acute Bothrops asper envenomation model (1-24 h) to contrast chronic versus acute inflammation. In the DMD model, we predicted phased cross-talk between sphingolipid metabolism and neurotrophin signaling: an early proteomic surge followed by lipid-mediated amplification and a late convergence at the protein level. Arginine and proline metabolism exhibited early metabolite accumulation preceding delayed inferred protein changes, consistent with impaired nitric oxide synthesis and argininemia-like effect. We also predicted late-stage activation of the AGE-RAGE pathway in DMD, likely triggered by ceramide buildup, and an autophagy-related lipid metabolic shift at mid-stage. In the envenomation model, tryptophan-kynurenine and nicotinamide pathways for NAD⁺ biosynthesis were rapidly perturbed at the metabolite level (1-3 h) but induced corresponding predicted enzymes only by 24 h. Thyroid hormone signaling showed an early coupling of substrate availability (tyrosine surge at 1 h) with predicted stress-response proteins and a second, delayed wave of inferred transcriptional regulators at 24 h. Acute envenomation also triggered immediate glycine/serine utilization possibly for antioxidant defense and glycerophospholipid breakdown (via phospholipase A₂), whereas chronic DMD showed sustained glycine/serine engagement and inferred, unresolved phospholipid perturbation without protein-level compensation, which may result from chronic oxidative stress. Overall, our integrative analysis revealed time-specific, multi-layer molecular perturbations distinguishing acute toxin injury from chronic muscle degeneration. Key metabolic control points (ceramide accumulation, arginine flux diversion, autophagy-lipid cross-talk, NAD⁺ salvage timing) were identified, highlighting potential targets for stage-specific therapeutic or nutritional interventions.

Animals↗

PubMed1979

A combined clinical and immunological assessment of four cyclophosphamide regimes in rheumatoid arthritis.

Four dosage regimes of cyclophosphamide have been compared in patients with late rheumatoid arthritis, in an attempt to separate toxicity from efficacy. Joint inflammation was assessed clinically and objectively by quantitative thermography. Delayed hypersensitivity in vitro was assessed using leucocyte migration inhibition (L.M.T.) to a standard antigen, Streptokinase. There was no significant difference in clinical response or side-effects between a continuous oral regime (1 mg/kg/day) and the same total dose given as an intermittent oral regime. Responders and non-responders were seen in both groups and there was a significant relationship between clinical response and fall in platelet count, suggesting a variable threshold. The same total dose given as an intermittent intravenous regime caused considerable side-effects but these could be avoided by the addition of methylprednisolone. Both intravenous regimes induced a much more rapid fall in the Thermographic Index (T.I.) than the oral regimes. Indeed many patients receiving oral cyclophosphamide showed an increase in joint inflammation in the first three weeks of treatment. Immunological studies demonstrated a corresponding increase in reactivity to Streptokinase over this period. There was a highly significant correlation between changes in L.M.T. and T.I. both early in treatment and, in the oral groups, over a period of six months.

Administration, Oral↗

PubMed1979

A comparative clinical and immunological assessment of methanol extraction residue of Bacillus Calmette-Guérin versus placebo in patients with advanced cancer.

Eighty-four patients with advanced cancer refractory to conventional therapeutic modalities were randomly assigned in double-blind fashion to one of three intradermal treatment regimens: "high"-dose methanol extraction residue fraction of Bacillus Calmette-Guérin (MER) (2.0 mg); "low"-dose MER (0.5 mg); or 0.9% NaCl solution placebo. Toxicity, consisting primarily of cutaneous inflammation and ulceration, was limited to patients receiving MER and was most severe with the high-dose regimen. Pretreatment clinical and immunological parameters were comparable between patient groups. Although a significant number of patients had increases in various immune parameters according to the criteria used, there was no appearent advantage to MER given in either dosage schedule compared to placebo. Patient survival was not affected by either MER regimen compared to placebo. This investigation failed to demonstrate any significant clinical or immunological benefit from MER given in two dosage regimens in patients with advanced cancer with the laboratory methodology used and emphasizes the importance of appropriate controls in evaluating immunostimulants in humans.

BCG Vaccine↗

PubMed1978

[The pathogenesis of psoriasis. Autoradiographic in vitro studies on cell proliferation in psoriasis vulgaris and other normal and hyperproliferative states of epidermal and dermal human cells].

In the epidermal cells of patients suffering from psoriasis we found a significant prolongation of DNA-synthesis time (ts) in uninvolved skin, very early lesions, and fully developed plaques. In uninvolved psoriatic skin ts in addition increased significantly within 6 hours after stripping of the horny layer. In normal epidermis and in other states of epidermal inflammation and hyperproliferation (akanthosis by petrolatum, toxic dermatitis, chronic allergic ekzema, neurodermitis, allergic patch test reaction) a comparable prolongation of ts was not ascertainable. This prolongation is most distinct in the early lesions and proceeds the development of hyperproliferation and akanthosis. A dermal infiltrate with increased proliferative activity seems to be a stimulus, in the sense of a Koebner-phenomenon. The abnormal psoriatic epidermis, with disturbed DNA-synthesis, reacts to this infiltrate as well as to other irritants not with a limited hyperproliferation but with the development of psoriatic plaque.

Autoradiography↗

PubMed1979

Pressure gun injection injuries of the hand.

In the growing number of pressure gun injuries with injection of materials into the hand, the degree of toxicity of the material, the amount injected and early adequate treatment are the three most important factors in determining the final result. Paint is the most toxic agent and causes an extreme amount of tissue inflammation. Early debridement of the injected material gives the best functional result. In spite of early surgical debridement, some of these injuries, most commonly with highly toxic agents, progress to eventual amputation.

Debridement↗

PubMed1977

Cytomegalovirus inclusions in patients with ulcerative colitis and toxic dilation requiring colonic resection.

Microscopic examination of 50 colon resection specimens from 46 patients with ulcerative colitis revealed 6 patients whose colons contained intranuclear inclusions characteristic for cytomegalovirus (CMV). All patients were male, 47 years of age or older, and all had marked severe and fulminating courses. Five of the 6 patients had toxic dilation of the colon. Three of our patients had received no steroid therapy before their toxic dilation, however, all received steroids during attempts at medical management. Two other patients were found to have toxic dilation of the colon among our 46 patients, however, no evidence of CMV could be found in these 2 cases. There were 6 patients without toxic dilation whose colon specimens showed destructive inflammation and granulation tissue extending into the muscularis propria or transmurally. None of the colons from these 6 patients contained CMV inclusions. In our patients, the finding of CMV may be coincidental, but it is suggested that in our group of patients with ulcerative colitis, the CMV may play a role in altering the clinical course of these patients.

Aged↗

PubMed1978

Environmental injury of the lung: role of humoral mediators.

Environmental lung injury may take the form of acute tracheobronchitis, asthma, pulmonary edema, chronic bronchitis, emphysema, allergic pneumonitis, fibrosing alveolitis, pleurisy, and neoplastic disease. Environmental factors eliciting these responses include irritant gases and fumes, oxidants, organic allergens, inorganic dust, bacterial enzymes, and high partial pressures of oxygen. The basic pulmonary reactions to these toxic agents--bronchoconstriction, vasoconstriction, increased vascular permeability, inflammation, carcinogenesis--may be mediated, aggravated, or modulated by biologically active substances. These humoral agents include biogenic amines (e.g. histamine): peptides (e.g., bradykinin, vasoactive intestinal peptide, and spasmogenic lung peptide); enzymes (e.g., proteases, superoxide dismutase, and mixed function oxidases); and acidic lipids (e.g., prostaglandins, prostaglandin endoperoxides, and thromboxanes).

Acute Disease↗

PubMed1979

[Biological and pharmacological effects of carrageenan (author's transl)].

Carrageenan is sulfated polysaccharide which has been extensively used as emulsifier and thickening agent in the food industry, for its ability to induce acute inflammation in pharmacology and for its selectively toxic effect for macrophages in immunology. Carrageenan is a complex substance which displays various biological properties. The authors have shown the extent of these actions and reviewed the latest investigations on this subject.

Animals↗

PubMed1978

Use of platelet-fibrinogen-thrombin mixture to seal experimental penetrating corneal wounds.

A platelet-fibrinogen-thrombin mixture utilizing autologous platelets was studied for its potential to seal perforating corneal wounds. In rabbits, the mixture demonstrated sufficient adhesive properties to permit 75% of penetrating keratoplasties to remain in place without the use of sutures. All 12 grafts held initially; after 48 h three grafts extruded. In control eyes only two out of 12 (16%) of the corneal grafts remained in place. The material is simple to prepare and apply and is not toxic to the cornea. It does not cause inflammation or lid irritation. Intraocular complications observed with its use were transient anterior synechiae and retrocorneal membrane formation.

Animals↗

PubMed1979

Investigations into the skin-irritant properties of resiniferonol ortho esters.

A series of esters were produced by partial synthesis from 9,13,14-orthophenylacetyl-resiniferonol. These compounds were tested for irritant effects by means of a mouse ear assay. All of the derivatives, including the parent compound, produced short-term inflammation of mice ears within 1-2 h and the effects did not persist for 24 h. This is in contrast to esters of structurally related tigliane diterpenes which produce a longer-term on mice ears. Highly potent irritants were synthesized which exhibited irritant doses 50% in the 0.0012-0.00021 nmol range. These esters were all substituted phenylacetates of the C-20 position of 9,13,14-orthophenylacethyl-resiniferonol. The meta or para positions of the phenylacetate moiety were substituted with electronegative groups for maximum activity. Compounds exhibiting substituted phenyl propionates at C20 were not irritants in the test used.

Animals↗

PubMed2026

Common xenobiotics modulate gut microbial responses to low‑calorie sweeteners in vitro.

The gut microbiota is implicated in adverse effects associated with low-calorie sweeteners. Yet, the direct impact of sweeteners on gut bacteria remains largely uncharacterized. Here, we report interactions between 25 phylogenetically diverse gut bacterial strains and 39 commercially used sweeteners. We tested these sweeteners individually and in combination with four commonly co-consumed compounds, viz., advantame, caffeine, vanillin, and duloxetine. Three-quarters of the tested sweeteners individually impacted the growth of at least one tested bacterial strain. Further, over 100 interactions were found between sweeteners and the four co-consumed compounds. Isosteviol, a commonly used sweetener-component, and duloxetine, an antidepressant, synergistically inhibited Roseburia intestinalis, a bacterium previously linked to glucose homeostasis, and Parabacteroides merdae, a prevalent commensal linked to healthy microbiota. Proteomic, metabolomic, and genetic analyses indicate altered small molecule transport underpinning this sweetener-drug synergy. The isosteviol-duloxetine combination also modulated metabolism of a synthetic gut bacterial community, leading to increased toxicity to HeLa cells and altered secretion of inflammation-modulatory cytokines IL-6 and IL-8 by Caco-2 cells. Our data warrant further studies on interactions between low-calorie sweeteners and common xenobiotics.

Humans↗

PubMed1977

Pathologic analysis of mink mortality in New England mink.

The underlying cause of death of a group of New England mink, which died in 1969 to 1970 was explored. PCB and chlorinated hydrocarbon pesticide levels were measured. Aroclor 1254 levels in these mink were elevated 73 fold over levels in healthy mink in 1974. DDT levels were elevated 5 times and DDE 3 times over those control animals. Gross pathology revealed desions of the lungs, liver and kidneys. There lesions were confirmed microscopically. The lungs of the New England mink showed inflammation and congestion. Areas of inflammation were also present in the liver. Massive areas of necrosis were seen in the kidneys, both in the medullary and cortical areas. Kidney involvement was greater than any other organ. P.A.S. positive material was seen in each of these organs with the kidneys showing largest amounts of this material. Since the New England mink did not show lesions of the G.I. tract, did not exhibit fatty degeneration of the liver, which PCB toxicity is known to induce in mink and because they showed areas of congestion, inflammation and positive P.A.S. material, PCB's were not considered the toxic agent. However, fungus or bacterial infection might be the causative agent.

Adipose Tissue↗

PubMed1979

An assay procedure for the comparative irritancy testing of esters in the tigliane and daphnane series.

A method is described for testing of diterpene esters for irritancy. The technique involves the application of acetone solutions of the toxins to the inside ears of female LACA mice. The number of mice responding per group and the log10 dose data were evaluated using probit analysis with the assistance of a computer program. This evaluation has the advantage that approximations inherent with an arithmetical evaluation were eliminated, and limits may be placed upon the standard deviation of the irritant dose 50% (ID50). In addition, the use of a chi2 test automatically eliminated results which were not attributed to random biological variation. Observations of the time to onset and the persistence of the inflammation have led to the suggestion that daphnane orthoester diterpenes may elicit their effect by means of a direct action at a receptor site in skin, whereas the tigliane O-acyl esters may in part act by causing more general tissue damage.

Animals↗

PubMed2026

Neurodevelopmental toxicity of 2-(Methylthio)benzothiazole (MTBT) in zebrafish: Insights into PTGS2- associated dysregulation of the neuroactive ligand-receptor interaction pathway.

2-(Methylthio)benzothiazole (MTBT), an important derivative of benzothiazoles, has extensive applications in industrial processes, pharmaceuticals, and environmental monitoring. It can enter aquatic environments through surface runoff and has been detected at relatively high concentrations in various environmental systems. However, studies investigating the aquatic toxicity of MTBT remain limited. In this study, zebrafish embryos were exposed to MTBT at concentrations of 0, 10, 100, and 1000 μg/L for 144 h to evaluate its developmental and neurotoxic effects. MTBT exposure significantly reduced the survival rate, hatching rate, spontaneous movement, and body length of zebrafish larvae. MTBT also impaired locomotor behavior, reduced fluorescence of Tg(huc:eGFP) larvae in the central nervous system and inhibited motor neuron axonal development. Protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that MTBT-induced neurotoxicity may be associated with disruption of the neuroactive ligand-receptor interaction pathway. Further validation experiments revealed that MTBT induced oxidative stress, inflammation, and apoptosis, suggesting that these adverse effects may underlie its neurodevelopmental toxicity. Collectively, these findings provide biological evidence that MTBT induces neurodevelopmental toxicity in zebrafish larvae and suggest that dysregulation of the PTGS2-related neuroactive ligand-receptor interaction pathway may be involved in this process.

2-(Methylthio)benzothiazole (MTBT)↗

PubMed1979

Gentian violet keratoconjunctivitis.

A case of bilateral keratoconjunctivitis caused by self-instillation of a 1% aqueous solution of gentian violet was complicated by a secondary uveitis and gram-negative conjunctivitis. The patient was treated with cycloplegics and specific antibiotics and after resolution of the bacterial infection, a mild topical corticosteroid was used. After six months the patient had completely recovered from the keratitis, but bilateral corneal vascularization, had unilateral posterior synechiae, corneal scarring, and cataract formation were present. Cationic dyes such as gentian violet appear to be toxic to the ocular surfaces and tend to produce severe intraocular inflammation.

Administration, Topical↗

PubMed1978

Type III (Arthus) allergic reactions and endotoxin toxicity in guinea-pigs.

Lipoplysaccharide (endotoxin) from E. coli cells produced lethal effects in guinea-pigs. Endotoxin caused no visible dermal change in normal animals, but produced skin reactions characterized by specific Arthus-type (Type III immune hypersensitivity) vascular inflammation in immunized animals. It is concluded that Arthus allergic reactions were evoked by endotoxin, however, endotoxin lethal toxicity appears independent of this process.

Animals↗