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International Archives of Allergy and... 2016Pyrazolones are the most common causes of selective nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. We studied a large group of patients with immediate and...
BACKGROUND
Pyrazolones are the most common causes of selective nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. We studied a large group of patients with immediate and delayed selective responses to metamizole.
METHODS
Patients with suspicion of hypersensitivity to metamizole were evaluated. We verified acetylsalicylic acid tolerance and classified patients as immediate or delayed responders if they showed symptoms less or more than 24 h after metamizole administration. Skin tests were performed and if negative, a basophil activation test (BAT) was performed on immediate responders. If it was negative, we performed a drug provocation test (DPT) with metamizole.
RESULTS
A total of 137 patients were included: 132 reacted within 24 h (single NSAID-induced urticaria/angioedema/anaphylaxis; SNIUAA) and 5 after 24 h (single NSAID-induced delayed hypersensitivity reaction; SNIDHR). Most SNIUAA patients developed anaphylaxis (60.60%); for SNIDHR, maculopapular exanthema was the most frequent entity (60%). Skin testing was positive in 62.04% of all cases and BAT in 28% of the SNIUAA patients with negative skin tests. In 5.1% of the cases, DPT with metamizole was needed to establish the diagnosis. In 22.62% of the cases, diagnosis was established by consistent and unequivocal history of repeated allergic episodes in spite of a negative skin test and BAT.
CONCLUSIONS
SNIUAA to metamizole is the most frequent type of selective NSAID hypersensitivity, with anaphylaxis being the most common clinical entity. It may occur within 1 h after drug intake. SNIDHR occurs in a very low percentage of cases. The low sensitivity of diagnostic tests may be due to incomplete characterization of the chemical structures of metamizole and its metabolites.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Anaphylaxis; Clinical Decision-Making; Dipyrone; Disease Management; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Male; Middle Aged; Phenotype; Skin Tests; Time Factors; Young Adult
PubMed: 27224978
DOI: 10.1159/000444798 -
Basic & Clinical Pharmacology &... Feb 2017In this MiniReview, we summarize the body of knowledge on the delayed-type hypersensitivity arthritis (DTHA) model, a recently developed arthritis model with 100%... (Review)
Review
In this MiniReview, we summarize the body of knowledge on the delayed-type hypersensitivity arthritis (DTHA) model, a recently developed arthritis model with 100% incidence, low variation and synchronized onset in C57BL/6 (B6) mice, and compare it to other murine arthritis models. It is desirable to have robust arthritis models in B6 mice, as many transgene strains are bred on this background. However, several of the most widely used mouse model of arthritis cannot be induced in B6 mice without the drawback of lower incidence, reduced severity and higher variation, if at all. DTHA is induced by modifying a classical methylated bovine serum albumin (mBSA)-induced DTH response by administering a cocktail of anti-type II collagen antibodies (anti-CII) between immunization and challenge. Arthritis affects one, predefined paw in which acute inflammation and severe arthritis rapidly develop and peak after 4-7 days. Disease is self-resolving over the course of around 3 weeks. Disease manifestations resemble those seen in other arthritis models and include bone erosion, cartilage destruction, oedema, pannus and new bone formation. Induction of DTHA is dependent on CD4 T cells while B cells are dispensable. The DTHA model is set apart from other murine arthritis models in that it can be induced in B6 mice with 100% incidence and with high and consistent severity. This is the clearest advantage of the model, as the mechanisms of disease and clinical manifestations can be found in other arthritis models. The model holds potential for future modifications that may improve the lack of chronicity.
Topics: Animals; Antibodies; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Collagen Type I; Hypersensitivity, Delayed; Joints; Mice, Inbred BALB C; Mice, Inbred C57BL; Serum Albumin, Bovine; Severity of Illness Index; Species Specificity; Time Factors
PubMed: 27553641
DOI: 10.1111/bcpt.12657 -
Arthritis Research & Therapy Jun 2012Rheumatoid arthritis (RA) is a chronic progressive, inflammatory and destructive autoimmune disease, characterised by synovial joint inflammation and bone erosion. To...
INTRODUCTION
Rheumatoid arthritis (RA) is a chronic progressive, inflammatory and destructive autoimmune disease, characterised by synovial joint inflammation and bone erosion. To better understand the pathophysiology and underlying immune mechanisms of RA various models of arthritis have been developed in different inbred strains of mice. Establishment of arthritis models with components of adaptive immunity in the C57BL/6J strain of mice has been difficult, and since most genetically modified mice are commonly bred on this background, there is a need to explore new ways of obtaining robust models of arthritis in this strain. This study was undertaken to establish and characterise a novel murine model of arthritis, the delayed-type hypersensitivity (DTH)-arthritis model, and evaluate whether disease can be treated with compounds currently used in the treatment of RA.
METHODS
DTH-arthritis was induced by eliciting a classical DTH reaction in one paw with methylated bovine serum albumin (mBSA), with the modification that a cocktail of type II collagen monoclonal antibodies was administered between the immunisation and challenge steps. Involved cell subsets and inflammatory mediators were analysed, and tissue sections evaluated histopathologically. Disease was treated prophylactically and therapeutically with compounds used in the treatment of RA.
RESULTS
We demonstrate that DTH-arthritis could be induced in C57BL/6 mice with paw swelling lasting for at least 28 days and that disease induction was dependent on CD4+ cells. We show that macrophages and neutrophils were heavily involved in the observed pathology and that a clear profile of inflammatory mediators associated with these cell subsets was induced locally. In addition, inflammatory markers were observed systemically. Furthermore, we demonstrate that disease could be both prevented and treated.
CONCLUSIONS
Our findings indicate that DTH-arthritis shares features with both collagen-induced arthritis (CIA) and human RA. DTH-arthritis is dependent on CD4+ cells for induction and can be successfully treated with TNFα-blocking biologics and dexamethasone. On the basis of our findings we believe that the DTH-arthritis model could hold potential in the preclinical screening of novel drugs targeting RA. The model is highly reproducible and has a high incidence rate with synchronised onset and progression, which strengthens its potential.
Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Enzyme-Linked Immunosorbent Assay; Hypersensitivity, Delayed; Immunohistochemistry; Mice; Mice, Inbred C57BL
PubMed: 22676339
DOI: 10.1186/ar3867 -
Scientific Reports Jan 2019Females have more robust immune responses than males, well-illustrated by the degree of inflammation elicited during delayed-type hypersensitivity (DTH) responses. Here,...
Females have more robust immune responses than males, well-illustrated by the degree of inflammation elicited during delayed-type hypersensitivity (DTH) responses. Here, we have investigated underlying sex differences that may contribute to differential footpad DTH responses using wildtype and four core genotypes (FCG) mice and popliteal lymphnode cellularity and gene expression. DTH responses in XX and XY FCG females showed no role for almost all genes expressed on sex chromosomes. After then filtering-out genes differentially expressed between XX and XY females, only one gene was sexually differentially expressed in wildtype mice, glycosylation-dependent cell adhesion molecule 1 (Glycam1), expressed 7-fold higher in females. Glycam1 facilitates leukocyte entry through high endothelial venules. Consistent with greater Glycam1 expression, female nodes contained twice as many cells. While females had more memory T cells in their nodes, males had a higher percentage of T regulatory cells. This sexual dimorphism in wildtype animals manifested pre-pubertally, was enhanced post-pubertally, and was eliminated by castration. The formation of male gonads is determined by the expression of Sry. Sry overexpression, which does not affect testosterone levels, produced an exaggerated male phenotype. We conclude that Sry expression through formation of the male gonad indirectly negatively impacts the potential for local inflammation.
Topics: Animals; Candida albicans; Cell Count; Female; Genes, sry; Gonads; Hypersensitivity, Delayed; Immunologic Memory; Lymph Nodes; Lymphocyte Count; Male; Mice, Inbred C57BL; Popliteal Artery; Sex Characteristics; Sexual Maturation; Spleen; T-Lymphocytes
PubMed: 30700819
DOI: 10.1038/s41598-018-37175-5 -
Physiology & Behavior Jan 2020Stable behavioral traits (temperament, personality) often predict health outcomes. Temperament-specific differences in immune function could explain temperament-specific...
Stable behavioral traits (temperament, personality) often predict health outcomes. Temperament-specific differences in immune function could explain temperament-specific health outcomes, however, we have limited information on whether immune function varies by personality. In the present study, we examined the relationship between a basic behavioral trait (behavioral-inhibition vs. non-inhibition) and two immune responses (innate inflammation and delayed-type hypersensitivity, DTH) in a rodent model. In humans, behavioral inhibition (fearful temperament) is associated with altered stress physiology and allergies. In laboratory rats, the trait is associated with elevated glucocorticoid production. We hypothesized that behavioral inhibition is associated with glucocorticoid resistance and dampened T-helper 1 cell responses often associated with chronic stress and allergies. Further, this immune profile would predict poorly-regulated innate inflammation and dampened DTH. In male Sprague-Dawley rats, we quantified consistent behavioral phenotypes by measuring latency to contact two kinds of novelty (object vs. social), then measured lipopolysaccharide(LPS)-induced innate inflammation or keyhole limpet hemocyanin(KLH)-induced DTH. Behaviorally-inhibited rats had heightened glucocorticoid and interleukin-6 responses to a low/moderate dose of LPS and reduced DTH swelling to KLH re-exposure compared to non-inhibited rats. These results suggest that behavioral inhibition is associated with a glucocorticoid resistant state with poorly regulated innate inflammation and dampened cell-mediated immune responses. This immune profile may be associated with exaggerated T-helper 2 responses, which could set the stage for an allergic/asthmatic/atopic predisposition in inhibited individuals. Human and animal models of temperament-specific immune responses represent an area for further exploration of mechanisms involved in individual differences in health.
Topics: Animals; Behavior, Animal; Glucocorticoids; Hemocyanins; Hypersensitivity, Delayed; Inflammation; Inhibition, Psychological; Interleukin-6; Lipopolysaccharides; Male; Phenotype; Rats; Temperament
PubMed: 31629765
DOI: 10.1016/j.physbeh.2019.112693 -
The American Journal of Pathology Jan 1978
Review
Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Autoimmune Diseases; Complement System Proteins; Female; Graft Rejection; Graft vs Host Reaction; Granuloma; Humans; Hypersensitivity; Hypersensitivity, Delayed; Immune System Diseases; Male; Pregnancy
PubMed: 23009
DOI: No ID Found -
Journal of Visualized Experiments : JoVE 2007Delayed type hypersensitivity (DTH) is an inflammatory reaction mediated by CCR7- effector memory T lymphocytes that infiltrate the site of injection of an antigen...
Delayed type hypersensitivity (DTH) is an inflammatory reaction mediated by CCR7- effector memory T lymphocytes that infiltrate the site of injection of an antigen against which the immune system has been primed. The inflammatory reaction is characterized by redness and swelling of the site of antigenic challenge. It is a convenient model to determine the in vivo efficacy of immunosuppressants. Cutaneous DTH can be induced either by adoptive transfer of antigen-specific T lymphocytes or by active immunization with an antigen, and subsequent intradermal challenge with the antigen to induce the inflammatory reaction in a given skin area. DTH responses can be induced to various antigens, for example ovalbumin, tuberculin, tetanus toxoid, or keyhole limpet hemocyanin (KLH).Here we demonstrate how to induce an active DTH reaction in Lewis rats. We will first prepare a water-in-oil emulsion of KLH, our antigen of interest, in complete Freund's adjuvant and inject this emulsion subcutaneously to rats. This will prime the immune system to develop memory T cells directed to KLH. Seven days later we will challenge the rats intradermally on the back with KLH on one side and with ovalbumin, an irrelevant antigen, on the other side. The inflammatory reaction will be visible 16-72 hours later and the red and swollen area will be measured as an indication of DTH severity.
Topics: Adjuvants, Immunologic; Animals; Dermatitis; Emulsions; Hemocyanins; Hypersensitivity, Delayed; Immunologic Memory; Injections, Intradermal; Injections, Subcutaneous; Rats; Rats, Inbred Lew; Severity of Illness Index; T-Lymphocytes; Time Factors
PubMed: 18997885
DOI: 10.3791/237 -
American Journal of Physical... Jun 2013We evaluated sex, age, nutritional status, and infectious disease (ID) as predictors of two biomarkers of cell-mediated immunity (CMI), delayed-type hypersensitivity to...
We evaluated sex, age, nutritional status, and infectious disease (ID) as predictors of two biomarkers of cell-mediated immunity (CMI), delayed-type hypersensitivity to Candida albicans (DTH-Candida), and anti-Epstein-Barr virus antibody (EBV Ab), among 200 children in Kilimanjaro, Tanzania. DTH-Candida, which decreases with compromised CMI, was positively associated with age (OR: 1.27; 95% CI: 1.02, 1.57) and triceps skinfold (TSF; OR: 1.16; 95% CI: 1.02, 1.26), and inversely associated with height-for-age Z score (HAZ; OR: 0.86; 95% CI: 0.68, 1.08) and diagnosed ID (OR: 0.48; 95% CI: 0.22, 1.08). There was significant interaction between TSF and ID: DTH-Candida exhibited a strong inverse association with ID among children with low TSF (OR: 0.16; 95% CI: 0.05, 0.50) and a strong positive association with TSF among children with ID (OR: 2.64; 95% CI: 1.29, 5.42). EBV Ab, which increases with compromised CMI, was inversely associated with male sex (β: -0.47; 95% CI: -0.70, -0.24) and TSF (β: -0.04; 95% CI: -0.08, 0.00), and positively associated with HAZ (β: 0.06; 95% CI: -0.03, 0.15). Among males, EBV Ab was positively associated with anemia. Among normal HAZ children, EBV Ab was inversely associated with TSF. There was no association between DTH-Candida and EBV Ab. While DTH-Candida provides a direct measure of CMI, our results suggest that interpretation of EBV-Ab among Kilimanjaro children was complicated by its indirect relationship with CMI. Among our sample, CMI increased with age and adequate nutrition and was compromised during acute ID. The suggestive CMI-compromising effect of increasing height-for-age may bear further exploration.
Topics: Analysis of Variance; Antibodies, Viral; Biomarkers; Candida albicans; Child; Child, Preschool; Cohort Studies; Dried Blood Spot Testing; Female; Herpesvirus 4, Human; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Linear Models; Male; Malnutrition; Skinfold Thickness; Tanzania
PubMed: 23460387
DOI: 10.1002/ajpa.22250 -
Journal of Investigational Allergology... Dec 2022
Topics: Humans; Salts; Drug Hypersensitivity; Desensitization, Immunologic; Hypersensitivity, Delayed; Iron
PubMed: 35118939
DOI: 10.18176/jiaci.0789 -
Environmental Health Perspectives Feb 1982A variety of in vivo and more recently in vitro assays have been described to assess cell mediated immunity (CMI). Two methods routinely employed in our laboratory to... (Review)
Review
A variety of in vivo and more recently in vitro assays have been described to assess cell mediated immunity (CMI). Two methods routinely employed in our laboratory to assess CMI following exposure to chemicals in rodents include delayed hypersensitivity and in vitro lymphoproliferation. Preliminary studies indicate that depressed delayed hypersensitivity responses, as performed by a radiometric assay, correlates with altered susceptibility to infectious agents and tumor cell challenge following exposure to immunotoxic chemicals. Furthermore, suppression of T-cell lymphoproliferative responses to at least 50% below control values correlated with depressed delayed hypersensitivity responses and altered host susceptibility. On the other hand, when suppression of T-cell lymphoproliferative responses are within 50% of control values, delayed hypersensitivity and host susceptibility parameters are not affected. Assuming adequate technical expertise and accurate data interpretation, CMI assays of these types can provide a valuable data base for toxicology studies and immunotoxicity assessment.
Topics: Animals; Cell Division; Humans; Hypersensitivity, Delayed; Immunity, Cellular; In Vitro Techniques; Lymphocytes; Toxicology
PubMed: 7037387
DOI: 10.1289/ehp.824331