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Travel Medicine and Infectious Disease 2023
Topics: Humans; Arthus Reaction; Vaccines; Vaccination; Adverse Drug Reaction Reporting Systems; Immunization
PubMed: 37797703
DOI: 10.1016/j.tmaid.2023.102647 -
Metabolites Aug 2023Pteropodine (PT) is a component of some plants with potentially useful pharmacological activities for humans. This compound has biomedical properties related to the...
Pteropodine (PT) is a component of some plants with potentially useful pharmacological activities for humans. This compound has biomedical properties related to the modulation of the immune system, nervous system, and inflammatory processes. This study addresses the anti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect of PT was evaluated by determining the myeloperoxidase enzyme activity. PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 51, 66 and 70% inhibitory effect of 10, 20 and 40 mg/kg of PT, respectively, in the rat paw edema test. In the pleurisy assay, 40 mg/kg of PT induced a low neutrophil count (up to 36%) when compared to the negative control group, and 20 mg/kg of PT increased the content of lymphocytes by up to 28% and the pleural exudate volume decreased by 52% when compared to the negative control group, respectively. We also found an 81.4% inflammatory inhibition of the edema ear with 0.04 mg/ear of PT, and a significant myeloperoxidase enzyme inhibition by the three doses of PT tested. We conclude that PT exerted a potent anti-inflammatory effect in the acute inflammation model in rodents.
PubMed: 37623851
DOI: 10.3390/metabo13080907 -
Biomolecules & Therapeutics Nov 2023Rhizome of has been used as a traditional medicine for treating kidney diseases in East Asian countries. Its inhibitory effects on hypersensitivity responses have been...
Rhizome of has been used as a traditional medicine for treating kidney diseases in East Asian countries. Its inhibitory effects on hypersensitivity responses have been reported for methanol extracts, with alisol B 23-acetate (AB23Ac) being the most active constituent among six terpenes in inhibiting the direct passive Arthus reaction. However, whether AB23Ac has efficacy against allergic asthma has not been tested to date. The efficacy of AB23Ac in an ovalbumin (OVA)-induced allergic asthma mouse model was evaluated by administrating AB23Ac before OVA sensitization or OVA challenge in BALB/c mice. AB23Ac suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of AB23Ac both before OVA sensitization and OVA challenge greatly lowered pulmonary resistance and the increase in immune cell counts and inflammatory responses around the peribronchial and perivascular regions. In addition, the inflammatory cytokine levels of Th1/Th2/Th17 cells in the bronchoalveolar lavage fluid decreased in the AB23Ac-treated groups. AB23Ac reduced the number of PAS-stained cells in the lungs. Furthermore, a computer modeling study indicated that AB23Ac can bind tightly to spleen tyrosine kinase (Syk). These results suggest that AB23Ac may ameliorate allergic asthma by suppressing immune responses in dendritic cells during sensitization and in mast cells during challenge periods.
PubMed: 37317820
DOI: 10.4062/biomolther.2023.032 -
Archives of Razi Institute Oct 2022causes a wide variety of infectious diseases. Lipopolysaccharide (LPS) is a large heat-stable polymer that is gram-negative bacteria's major outer membrane component,...
causes a wide variety of infectious diseases. Lipopolysaccharide (LPS) is a large heat-stable polymer that is gram-negative bacteria's major outer membrane component, accounting for roughly 75% of the surface area and 5-10% of the total dry weight. Therefore the current study was carried out to investigate the immunomodulatory effect of purified lipopolysaccharide produced from local clinical isolates compared with ZnO-NPs and LPS-ZnO NPs. To do the experimental evaluations 35, Balb/c mouse was injected intramuscularly (i.m.) with different concentrations of the purified LPS, ZnoNPs and LPS-ZnoNPs for 12 days and immunized with 10% SRBCs (i.p) on day 4 and 8 of the schedule, while suspension and normal saline for positive and negative control groups. Focus on estimating body weight before and after treatment, Arthus and delayed-type hypersensitivity, and detecting serum level of cytokines (TLR-2, IL1Beta, IL4, and IL10) using sandwich ELISA. The data showed the highest value before and after treatment with LPS-ZnO NPs recorded in 2µg/mouse was 27. 92±1.48 and 31.50±0.4, respectively. In Arthurs reaction and Delayed type hypersensitivity, the highest results showed in the positive control group injected with 4.08±0.17 and 4.86±80.02, respectively. The results of TLR-2 showed the highest value in the positive control group, 242.17±3.98 pg/ml, followed by Group LPS at 135.51.58 pg/ml. The results of Interleukin-1Beta showed the highest value in the positive control group, 254.88±3.51 pg/ml, followed by Group LPS 174.3± 1.46 pg/ml. The concentration of IL-4 in serum of treated albino mice showed the highest value in the positive control group, 136.2±1.12 pg/ml, followed by Group LPS 86.12±1.49 pg/ml. While the highest value of IL-10 was recorded in the positive control group, 98.58± 4.09 pg/ml, followed by Group LPS- ZnoNP in concentration 4µg/ mouse was 86.018±0.69 pg/ml. The results of the statistical analysis showed a significant difference (≤0.05) between LPS, ZnoNPs, and LPs-ZnoNPs treated groups and control groups (positive & negative). In the present study, we can conclude that LPS-ZnO NPs had a positive immunomodulatory effect on immune response in immunized mice. As shown in the results of the level of IL-1 beta, IL-4, IL-10, and TLRs-2, Abs titer, and Arthus and DTH reactions.
Topics: Mice; Animals; Zinc Oxide; Lipopolysaccharides; Interleukin-10; Toll-Like Receptor 2; Interleukin-4; Nanoparticles; Immunity
PubMed: 37123110
DOI: 10.22092/ARI.2022.358493.2233 -
Clinics in Dermatology 2022Cutaneous leukocytoclastic vasculitis (LCV) has a distinctive clinical and light microscopic presentation; however, the etiologic basis of LCV is varied. Most cases are...
Cutaneous leukocytoclastic vasculitis (LCV) has a distinctive clinical and light microscopic presentation; however, the etiologic basis of LCV is varied. Most cases are attributable to immune complex deposition within a vessel wall and represent an Arthus type III immune complex reaction. The prototypic immunoreactant profile is characterized by granular deposits of components of complement activation in concert with immunoglobulin within the cutaneous vasculature. We encountered nine patients with vasculitic and/or vesiculobullous clinical presentations exhibiting an LCV in association with an immunoreactant profile characterized by homogeneous linear deposits of immunoglobulin along the dermal epidermal junction in a fashion resembling an autoimmune vesiculobullous disease. Among the clinical presentations were palpable purpura, urticarial vasculitis, and vesiculobullous eruptions with supervening purpura. Two patients with Crohn disease presented with classic palpable purpura with biopsy-proven LCV, and direct immunofluorescence (DIF) studies demonstrated linear immunoglobulin G (IgG) with floor localization on the salt-split skin assay. Four patients with systemic lupus erythematosus (SLE) showed purpuric vesiculobullous lesions, with evidence of a neutrophilic interface dermatitis and LCV in three of the four. The remaining patient had urticarial nonbullous lesions showing small-vessel vasculitiswith a neutrophilic interface dermatitis. In all of the patients with SLE, DIF studies showed linear immunoglobulin deposits within the basement membrane zone (BMZ). These constellation of findings clinically, light microscopically, and by immunofluorescence were those of a vasculitic presentation of bullous systemic lupus erythematosus. Two patients had linear IgA disease, which was drug induced in one and paraneoplastic in the other, and the dominant morphology on biopsy in both cases was an LCV. One patient microscopically demonstrated drug-associated and eosinophilic enriched LCV with DIF studies showing striking linear deposits of IgG suggestive of bullous pemphigoid, which was consistent with a vasculitic presentation of drug-induced bullous pemphigoid. In all cases, typical granular vascular immunoglobulin and complement deposition compatible with immune complex mediated vasculitis was observed. It is likely that local immune complexes derived from BMZ antigen bound to antibody are pathogenically relevant. We propose the designation of linear vasculitis for this unique scenario of LCV and linear immunoglobulin epidermal BMZ staining, which in some cases represents a vasculitic presentation of conventional autoimmune vesiculobullous disease.
Topics: Humans; Vasculitis, Leukocytoclastic, Cutaneous; Antigen-Antibody Complex; Vasculitis; Skin; Immunoglobulin G; Urticaria; Dermatitis; Autoimmune Diseases; Basement Membrane; Lupus Erythematosus, Systemic
PubMed: 35907580
DOI: 10.1016/j.clindermatol.2022.07.011 -
Clinics in Dermatology 2021A total of 22 patients who had developed an adverse cutaneous reaction to the Moderna or Pfizer vaccine underwent biopsies. Each patient was assessed light...
A total of 22 patients who had developed an adverse cutaneous reaction to the Moderna or Pfizer vaccine underwent biopsies. Each patient was assessed light microscopically, and, in select biopsies, spike glycoprotein and cytokine assessment were also conducted. The patients developed self-limited cutaneous reactions often described clinically as urticarial or eczematous within 1 day to 4 weeks after receiving the first or second dose of the Pfizer or Moderna vaccine. Classic clinical and morphologic depictions of type IV cutaneous hypersensitivity with features of eczematous dermatitis, interface dermatitis, granulomatous inflammation, and/or lymphocytic vasculitic component were observed. Clinical and/or histologic features of perniosis, pityriasis rosea, pityriasis rubra pilaris, and guttate psoriasis were seen in select cases. In 2 cases the dominant picture was urticarial vasculitis, possibly reflective of an Arthus type III immune complex action. The biopsy specimens of normal skin post vaccine and of skin affected by the post-vaccine eruption showed rare deep microvessels positive for spike glycoprotein with no complement deposition contrasting with greater vascular deposition of spike protein and complement in skin biopsies from patients experiencing severe coronavirus disease 2019 (COVID-19). It is concluded that self-limited hypersensitivity reactions to the vaccine occur possibly owing to a substance found in the vaccine vehicle (eg, polyethylene glycol). An immune response that is directed against human-manufactured spike has to be considered because some of the reactions clinically and or histologically closely resemble mild COVID-19. Finally, vaccine-associated immune enhancement largely attributable to the adjuvant properties of the vaccine may unmask certain inflammatory milieus operational in psoriasis, atopic dermatitis, and subclinical hypersensitivity.
Topics: COVID-19; COVID-19 Vaccines; Eczema; Humans; SARS-CoV-2; Urticaria
PubMed: 34920834
DOI: 10.1016/j.clindermatol.2021.07.011 -
ImmunoHorizons Jul 2021The expression of Bruton tyrosine kinase (BTK) in B cells and innate immune cells provides essential downstream signaling for BCR, Fc receptors, and other innate immune...
The expression of Bruton tyrosine kinase (BTK) in B cells and innate immune cells provides essential downstream signaling for BCR, Fc receptors, and other innate immune cell pathways. The topical covalent BTK inhibitor PRN473 has shown durable, reversible BTK occupancy with rapid on-rate and slow off-rate binding kinetics and long residence time, resulting in prolonged, localized efficacy with low systemic exposure in vivo. Mechanisms of PRN473 include inhibition of IgE (FcεR)-mediated activation of mast cells and basophils, IgG (FcγR)-mediated activation of monocytes, and neutrophil migration. In vivo, oral PRN473 was efficacious and well tolerated in the treatment of canine pemphigus foliaceus. In this study, we evaluated in vitro selectivity and functionality, in vivo skin Ab inflammatory responses, and systemic pharmacology with topically administered PRN473. Significant dose-dependent inhibition of IgG-mediated passive Arthus reaction in rats was observed with topical PRN473 and was maintained when given 16 h prior to challenge, reinforcing extended activity with once-daily administration. Similarly, topical PRN473 resulted in significant dose-dependent inhibition of the mouse passive cutaneous anaphylaxis IgE-mediated reaction. Multiday treatment with topical PRN473 in rodents resulted in low-to-no systemic accumulation, suggesting that efficacy was mainly due to localized exposure. Reduced skin Ab inflammatory activity was also confirmed with oral PRN473. These preclinical studies provide a strong biologic basis for targeting innate immune cell responses locally in the skin, with rapid onset of action following once-daily topical PRN473 administration and minimal systemic exposure. Dose-dependent inhibition in these preclinical models of immune-mediated skin diseases support future clinical studies.
Topics: Animals; Female; Humans; Mice; Rats; Administration, Cutaneous; Administration, Oral; Agammaglobulinaemia Tyrosine Kinase; Arthus Reaction; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Passive Cutaneous Anaphylaxis; Protein Kinase Inhibitors; Skin; Skin Diseases
PubMed: 34326199
DOI: 10.4049/immunohorizons.2100063 -
Journal of Immunology (Baltimore, Md. :... Apr 2021Bruton tyrosine kinase (BTK) is expressed in B cells and innate immune cells, acting as an essential signaling element in multiple immune cell pathways. Selective BTK...
Bruton tyrosine kinase (BTK) is expressed in B cells and innate immune cells, acting as an essential signaling element in multiple immune cell pathways. Selective BTK inhibition has the potential to target multiple immune-mediated disease pathways. Rilzabrutinib is an oral, reversible, covalent BTK inhibitor designed for immune-mediated diseases. We examined the pharmacodynamic profile of rilzabrutinib and its preclinical mechanisms of action. In addition to potent and selective BTK enzyme and cellular activity, rilzabrutinib inhibited activation and inflammatory activities of B cells and innate cells such as macrophages, basophils, mast cells, and neutrophils, without cell death (in human and rodent assay systems). Rilzabrutinib demonstrated dose-dependent improvement of clinical scores and joint pathology in a rat model of collagen-induced arthritis and demonstrated reductions in autoantibody-mediated FcγR signaling in vitro and in vivo, with blockade of rat Arthus reaction, kidney protection in mouse Ab-induced nephritis, and reduction in platelet loss in mouse immune thrombocytopenia. Additionally, rilzabrutinib inhibited IgE-mediated, FcεR-dependent immune mechanisms in human basophils and mast cell-dependent mouse models. In canines with naturally occurring pemphigus, rilzabrutinib treatment resulted in rapid clinical improvement demonstrated by anti-inflammatory effects visible within 2 wk and all animals proceeding to complete or substantial disease control. Rilzabrutinib is characterized by reversible covalent BTK binding, long BTK residence time with low systemic exposure, and multiple mechanistic and biological effects on immune cells. Rilzabrutinib's unique characteristics and promising efficacy and safety profile support clinical development of rilzabrutinib for a broad array of immune-mediated diseases.
Topics: Agammaglobulinaemia Tyrosine Kinase; Animals; Anti-Inflammatory Agents; Basophils; Blood Platelets; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Humans; Immunoglobulin E; Kidney; Mast Cells; Mice; Mice, 129 Strain; Nephritis; Pemphigus; Protein Kinase Inhibitors; Purpura, Thrombocytopenic, Idiopathic
PubMed: 33674445
DOI: 10.4049/jimmunol.2001130 -
Frontiers in Immunology 2020In our previous study, we have found increased serum levels of HMGB1 in patients with Henoch- Schonlein purpura (HSP), allergic vasculitis (AV), and urticarial...
In our previous study, we have found increased serum levels of HMGB1 in patients with Henoch- Schonlein purpura (HSP), allergic vasculitis (AV), and urticarial vasculitis (UV) and altered HMGB1 distribution in lesional skin in patients with HSP. HMGB1 plays a pro-inflammatory role in the pathogenesis of HSP. To further investigate the role of HMGB1 in the pathogenic mechanism of vasculitis, we investigated the anti-inflammatory effects of HMGB1 blockades (including anti-HMGB1 mAb and glycyrrhizin) in a mouse model of a cutaneous reverse passive Arthus (RPA) reaction. A total of 36 balb/c mice were randomly divided into four groups: the control group, IC model group, HMGB1 monoclonal antibody (anti-HMGB1-mAb) group and the glycyrrhizin group, with nine mice in each group. A cutaneous RPA reaction mouse model was established by injections of the OVA antibody and the OVA antigen. Mice of the anti-HMGB1-mAb group and glycyrrhizin group were pre-treated with anti-HMGB1 mAb or glycyrrhizin, respectively, before the RPA reaction. Our results indicated that HMGB1 blockades (anti-HMGB1 mAb and glycyrrhizin) obviously extenuated the severity of vasculitis skin damage and improved the histological evolvement of inflammatory cells infiltration, vascular fibroid necrosis, and vasodilation in a cutaneous RPA reaction mouse model. In addition, HMGB1 blockades reduced the infiltration of neutrophils, DCs, and T cells and decreased the mRNA expression of IL-6 and CCL5 in skin lesions in the cutaneous RPA reaction mouse model. We suggest that HMGB1 blockades may represent a new direction for the treatment of cutaneous vasculitis.
Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Cytokines; Disease Models, Animal; Disease Susceptibility; Gene Expression; Glycyrrhizic Acid; HMGB1 Protein; Immunohistochemistry; Mice; Vasculitis, Leukocytoclastic, Cutaneous
PubMed: 33133061
DOI: 10.3389/fimmu.2020.02032