Pathophysiology of the inflammatory response

doi:10.1016/S0091-6749(99)70308-8

Journal of Allergy and Clinical Immunology

Volume 104, Issue 4, October 1999, Pages s132-s137

https://doi.org/10.1016/S0091-6749(99)70308-8 Get rights and content

Abstract

Airway allergic reactions enlist diverse cells and a multitude of chemical mediators that are responsible for the clinical symptoms of allergic rhinitis and asthma. Experiments in vitro and in animal models, as well as increasingly numerous studies in atopic human subjects, are revealing that an orchestrated continuum of cellular activities leading to airway allergic inflammation is set in motion in genetically predisposed individuals at the first exposure to a novel antigen. This sensitization step likely depends on differentiation of and cytokine release by T_H2 lymphocytes. Among T_H2-derived cytokines, IL-4 potently enhances B-lymphocyte generation of immunoglobulin E antibodies. The attachment of these antibodies to specific receptors on airway mast cells sets the stage for an acute inflammatory response on subsequent antigen exposure because IgE cross-linking by a bound antigen activates mast cells to release numerous inflammatory mediators. These mast cell–derived mediators collectively produce acute-phase clinical symptoms by enhancing vascular leak, bronchospasm, and activation of nociceptive neurons linked to parasympathetic reflexes. Simultaneously, some mast cell mediators up-regulate expression on endothelial cells of adhesion molecules for leukocytes (eosinophils, but also basophils and lymphocytes), which are key elements in the late-phase allergic response. Chemoattractant molecules released during the acute phase draw these leukocytes to airways during a relatively symptom-free recruitment phase, where they later release a plethora of cytokines and tissue-damaging proteases that herald a second wave of airway inflammatory trauma (late-phase response). The repetition of these processes, with the possible establishment in airway mucosa of memory T lymphocytes and eosinophils that are maintained by paracrine and autocrine cytokine stimulation, may account for airway hypersensitivity and chronic airway symptoms. (J Allergy Clin Immunol 1999;104:S132-7.)

Section snippets

AIRWAY ATOPY: A CONTINUUM OF CELLULAR RESPONSES

It is believed that individuals who express allergic symptoms are subject to an orchestration of cellular responses that commences with exposure to a specific antigen. The current model proposes that the potential for these responses is established with the first exposure to the antigen (sensitization), particularly in people with certain MHC alleles and other genetic predispositions.⁴ During this exposure several cellular players are recruited, both in terms of differentiation from inactive or

CONCLUSION

This brief consideration of the most well-documented cellular events that underlie atopic airway diseases illustrates the complexity and interrelatedness of several lines of response. Temporally, the immediate clinical symptoms of airway edema, constriction, and glandular secretion rapidly follow the allergen-triggered release of potent chemical mediators from mast cells in situ, whereas the late-phase responses of mucus secretion, bronchoconstriction, and airway hypersensitivity are conducted

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Fifty-one species from thirty-five countries were identified for their uses against inflammation. Twenty-four of such conditions were discernible, of which their applicability in wound healing and pain management was most conspicuous. The utilization of all plant parts was apparent, preparations of which were used primarily via topical application. Extracts of seventy-three species (from twenty-three genera) were examined in nearly thirty inflammation-based assays where their activities in vitro and in vivo were shown to be significant. They were effective in vivo against pain and swelling as well as wound healing, without detriment towards test subjects. The in vitro studies were carried out mainly in mononuclear cells such as macrophages, leukocytes, lymphocytes and neutrophils against which their cytotoxic effects were seen to be minimal. The modes of operation were shown to involve modulation of both pro-inflammatory (such as NF-κB, TNF-α, IL-6, IFN-γ, COX and NO) and anti-inflammatory (such as IL-10) factors.
The Amaryllidaceae is showcased as a platform highly conducive towards studies in the inflammation arena. Potent activities in instances were observed via in vitro and in vivo models of study, bolstered by the significant amounts of information emerging from traditional forms of medicine. It is conceivable that the family may yield future anti-inflammatory chemotherapeutics, particularly those related to its alkaloid principles.
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Current results indicated that SA could revere OVA-induced alteration in the inflammatory cell numbers, Th2 cytokines and IgE levels as well as histological changes in the bronchial airways and lung tissue. This results in line with previous studies indicating the infiltration of inflammatory cells including of lymphocytes, eosinophils, macrophages, and neutrophils into the bronchial lumen in OVA-induced allergic asthma; this results in the airway inflammation [18,19]. Particularly, eosinophils recognize as markers of allergic airway inflammation in asthma which act as the primary effector cells through generating of free radicals and specific granule proteins [20].
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Treatment with SA significantly inhibited inflammatory cell infiltration, enhanced IFN-γ level and decreased IL-4, IL-5 and IL-13 levels in BALF. Serum total and OVA-specific IgE levels and NO level in lung tissue were significantly reduced by SA. Histological examination demonstrated that SA significantly attenuated inflammatory cell infiltration and mucus-producing cells in the lung.
These data suggest that SA may be a new therapeutic potential to treat allergic asthma through suppressing T-helper 2 immune responses.
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To clarify the detailed molecular mechanisms underlying the development of asthma, we assessed the potential immune effects of prenatal osteoprotegerin (OPG) inhibition in the pathogenesis of asthma. The effects of OPG deficiency on the development of asthma were evaluated using an ovalbumin-induced asthma model in OPG knockout mice. Histological analysis demonstrated that OPG was mainly detected in airway epithelial cells in wild type mice. After ovalbumin sensitization and challenge, accumulation of inflammatory cells, gene expression of T helper 2-related cytokines and mucus hypersecretion in lung tissues were inhibited by OPG deficiency. Importantly, the serum level of IgE was not increased in OPG KO mice after ovalbumin sensitization and challenge. Based on these findings, OPG knockout mice were protected against methacholine-induced airway hyperresponsiveness. OPG expression is thought to be essential for induction of the allergic immune response in asthma.
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The pathophysiology of inflammatory process involves activation of monocyte cells which further initiate cascade of pro-inflammatory signaling pathways leading to regulation of downstream transcriptional factors such as nuclear factor kappa B (NF-ĸB) and interferon regulatory factor 1 (IRF-1). These factors induce expression of pro-inflammatory cytokines such as interleukin (IL) including IL-1, IL-1β, IL-6 and tumor necrosis factor-α (TNF-α) (Ashley et al., 2012; Jangpangi, 2016; Menkin, 1936; Pearlman, 1999; Vinaya, 2013). These inflammatory mediators are involved in pathogenesis of various diseases such as rheumatoid arthritis (RA), ulcerative colitis (UC), cardiovascular diseases, bacterial infections, depression, obesity, Parkinson disease (PD), nephrotic syndrome, cancer and diabetes (Chen et al., 2018; Donath et al., 2019; Higgins et al., 2003; Ito et al., 2019; Jangpangi, 2016; Juhn et al., 2008; Okin and Medzhitov, 2012; Rodríguez-Hernández et al., 2013; Sonsin-Diaz et al., 2019).
Inflammation, an important event of cellular defensive system, can be triggered by a variety of factors such as pathogens, allergens, damaged cells and toxic compounds. Inflammation indicates tissue remodeling and repair, and is characterized by redness, heat, swelling, pain and loss of function.
Conventional treatment approaches for treatment of inflammation/mediated disorders are associated with various side effects. Herbal remedies are comparatively safe with few side effects. Therefore, the current review summarizes different phytoconstituents which have exhibited their anti-inflammatory potential in various preclinical studies.
Google, PubMed, Web of Science and Scopus database have been searched for potentially relevant literature on plant based anti-inflammatory agents. Search was performed using different key words such as “inflammation”, “herbal drugs”, “anti-inflammatory drugs”, “phytomedicine for inflammation” and “plant derived drugs for inflammation”. Further studies were screened through assessment of abstracts and previously published review articles.
A number of natural products are reported to exhibit anti-inflammatory property in various preclinical and clinical studies and some of them are currently available as herbal formulations. Prominent phytoconstituents exhibiting anti-inflammatory activity include shagoal (Zingiber officinale Roscoe), curcumin (Curcuma longa L.), boswellic acid (Boswellia serrata Roxb.), quercetin (Allium cepa L.), rosmarinic acid (Rosmarinus officinalis L.), berberine (Coptis chinensis Franch) and catechin (Camellia sinensis (L.) Kuntze).
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Cysteine ameliorates allergic inflammatory reactions by suppressing thymic stromal lymphopoietin production in activated human mast cells
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Thymic stromal lymphopoietin (TSLP) derived by mast cells is recognized as a critical factor in many allergic inflammatory disorders. Cysteine is a well-known amino acid which exhibits anti-inflammatory activities. However, the effect and mechanism of cysteine on TSLP production have not been investigated. Thus, we hypothesized that cysteine may regulate TSLP production from mast cells. To test this hypothesis, the anti-inflammatory effects and signaling pathways of cysteine were investigated in phorbol 12-myristate 13-acetate 4 and calcium ionophore A23187 (PMACI)–stimulated human mast cell line HMC-1. Cysteine dramatically attenuated the levels of TSLP of both mRNA and protein without cytotoxicity. Moreover, cysteine suppressed caspase-1 activation and nuclear factor–κB translocation. The phosphorylation of p38 and c-Jun N-terminal kinase was downregulated in all cases in PMACI-stimulated HMC-1 cells treated with cysteine. In addition, cysteine decreased PMACI-induced proinflammatory cytokines in terms of both protein and mRNA levels. In conclusion, cysteine regulates TSLP production by blocking caspase-1, nuclear factor–κB, p38, and c-Jun N-terminal kinase–dependent pathways in activated HMC-1 cells, suggesting its potential as a regulator of allergic inflammatory diseases.
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By chromatographic separation on Sephadex^® LH-20 high- and low-molecular weight tannins were separated from OBD and the tannin composition analyzed by HPLC(DAD)-MSⁿ. Then, the OBD and its fractions were tested in degranulation (β-hexosaminidase activity) of allergen-specific-activated basophilic cells in a photometric assay.
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^☆: Supported by an unrestricted educational grant from Schering/Key Pharmaceuticals, Schering Corporation.

^☆☆: Reprint requests: David S. Pearlman, MD, Colorado Allergy and Asthma Clinic, 1450 S Havana, Suite 621, Aurora, CO 80012-4030.

^★: 0091-6749/99 $8.00 + 0 1/0/101682

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Pathophysiology of the inflammatory response☆,☆☆,★

Abstract

Section snippets

AIRWAY ATOPY: A CONTINUUM OF CELLULAR RESPONSES

CONCLUSION

Ann Allergy Asthma Immunol

Mol Genet Metab

Immunobiology

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Clin Chest Med

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Immunol Lett

J Allergy Clin Immunol

Allergic rhinitis: offering relief this season

J Respir Dis

Rhinitis and inhalant allergens

JAMA

Mechanisms of persistent airway inflammation in asthma: a role for T cells and T-cell products

Am J Respir Crit Care Med

IL-4 plays a dominant role in the differential development of TH0 into TH1 and TH2 cells

J Immunol

IL-4 plays a dominant role in the differential development of T_H0 into T_H1 and T_H2 cells