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Pathophysiology of Atopic Dermatitis and Atopiform Dermatitis
Published in Donald Rudikoff, Steven R. Cohen, Noah Scheinfeld, Atopic Dermatitis and Eczematous Disorders, 2014
A number of eosinophil-attracting cytokines are responsible for the trafficking of these cells to sites of cutaneous inflammation. These include IL-5, IL-8, RANTES, eotaxin, eotaxin-2, eotaxin-3, monocyte chemoattractant protein (MCP)-3, MCP-4 and TNF-α (Lampinen et al. 2004). Th2, mast, and epithelial cells are important sources of many of these mediators, and it is now recognized that eosinophils themselves produce many cytokines and play an important role in immunoregulation. Recently, the pluripotential cytokine macrophage migration inhibitory factor (MIF), which is expressed at higher levels in the skin and blood of patients with AD, has been proposed as a major factor causing eosinophil accumulation in the skin (Yoshihisa et al. 2010).
Local mucosal allergic disease
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Ibon Eguiluz-Gracia, Paloma Campo, Carmen Rondón
Asthma has been classified historically into allergic and nonallergic phenotypes, based on classical biomarkers such as SPT and serum sIgE. Nevertheless, several studies show that this dichotomy is not accompanied by a distinct inflammatory pattern, as multiple similarities exist in the bronchial infiltrate of allergic and nonallergic asthma [52,53]. Both phenotypes are characterized by the increased expression of IL-4, IL-5, IL-13, eotaxin-1, eotaxin-2, monocyte chemotactic proteins (MCP)-3 and -4, and CCR3, among other mediators [52,54]. Similar to rhinitis, mucosal IgE is suspected to play an important role in asthma, and there is ample evidence for local IgE synthesis in asthmatic patients regardless of their atopic status. Several studies demonstrate that nonatopic asthmatics display markers of εCSR and increased expression of FcεRI in the bronchial mucosa [53,55]. Interestingly, local IgE production may have a greater influence on the clinical outcomes of asthma than the systemic biomarkers of atopy [56]. Nevertheless, the specificity and affinity of mucosal IgE in asthma patients have not been sufficiently investigated, and it is unknown whether bronchial IgE can bind to environmental allergens as demonstrated for nasal IgE in AR and LAR individuals. Even though one study described functional HDM-sIgE in sputum samples from nonatopic asthmatics, the studied individuals failed to experience a positive bronchial allergen challenge. Therefore, the clinical relevance of neither the allergen nor the sIgE could be confirmed. Another study examining bronchial biopsies from atopic and nonatopic asthmatics showed that only atopic individuals had detectable bronchial sIgE [57]. In conclusion, even though εCSR can occur in the bronchial mucosa of all asthmatics regardless of their atopic status, the IgE involvement in the immunopathology of the nonatopic asthma phenotypes is not confirmed.
Plasma pro- and anti-inflammatory cytokines may relate to cocaine use, cognitive functioning, and depressive symptoms in cocaine use disorder
Published in The American Journal of Drug and Alcohol Abuse, 2021
Sydney N. Stamatovich, Paula Lopez-Gamundi, Robert Suchting, Gabriela D. Colpo, Consuelo Walss-Bass, Scott D. Lane, Joy M. Schmitz, Margaret C. Wardle
For cognition, two predominantly pro-inflammatory cytokines were selected: Eotaxin-2 CCL24 and TWEAK. These cytokines related to better overall cognitive performance, again inconsistent with our original hypothesis. Eotaxin-2 CCL24 was the most highly selected cytokine overall, being identified in >80% of models. Eotaxin-2 CCL24 is another member of the CC chemokine family, and is associated with aspirin-exaggerated respiratory disease (AERD) (69). A small number of studies suggest that it is also associated with psychiatric disorders. In particular, lower levels of Eotaxin-2 CCL24 are associated with bipolar disorder, although levels are elevated in individuals with major depressive disorder (70,71). Research on the broader Eotaxin family suggests that this family plays a role in cognition and neurodegeneration. Eotaxin-1 CCL11 and CCL26 are elevated in Alzheimer’s and Huntington’s diseases, and as noted above, Eotaxin-1 CCL11 related to poorer cognition in methamphetamine users; however, there are no prior findings suggesting that Eotaxin-2 CLL24 has the same impact (72,73). TWEAK is part of the pro-inflammatory TNF superfamily and plays a significant role in apoptosis, elevation of B cells, transplant rejection, and cell proliferation. Lower levels of TWEAK were found in crack cocaine-dependent women compared to a healthy control group (74). Thus, the relationship between higher levels of TWEAK and better cognitive performance on the Shipley-2 is more in line with previous research, despite its status as a pro-inflammatory marker.
IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils
Published in OncoImmunology, 2020
Melanie Kienzl, Carina Hasenoehrl, Paulina Valadez-Cosmes, Kathrin Maitz, Arailym Sarsembayeva, Eva Sturm, Akos Heinemann, Julia Kargl, Rudolf Schicho
Eosinophil migration assays were performed using 5 µm trans-well plates (Corning; CLS3387-8EA) as previously described by us.37 In brief, 1 × 105 IL-33 Eos (or IL-5 Eos) were put in the upper well. Supernatant from CT26 cell lines (conditioned for four days) and unconditioned medium was used for chemoattraction in the lower well. Recombinant CCL24 (eotaxin-2; Immunotools; # 11344174) was used as a positive control for eosinophil migration at the indicated concentrations. Eosinophils that migrated to the lower well were enumerated on a FACS Canto (BD Biosciences) as described previously.38
Precision medicine in chronic rhinosinusitis – using endotype and endotype-driven therapeutic options
Published in Expert Review of Clinical Immunology, 2023
Yutong Sima, Yan Zhao, Xiangdong Wang, Luo Zhang
Dupilumab was the first mAb for which a phase III clinical trial with CRS patients was completed, where it demonstrated powerful efficacy and safety [55,56]. The least squares mean difference in the nasal polyp score (NPS) decreased from 1.80 to 2.06 in week 24 and to 2.40 in week 52 compared with the baseline. Another main evaluation indicator, the nasal congestion score, improved from 0.87 to 0.89 points in week 24 and to 0.98 points in week 52. The sense of smell in CRS patients rapidly and sustainably improved, as indicated by both the loss of smell and smell test scores [55,57]. The Sinonasal Outcome Test-22 (SNOT-22 score also changed from 17.36 to 30.43 in week 24 and to 20.96 in week 52 [55]. Patient-reported outcomes measured using the EuroQol 5D (ED-5Q) Visual Analog Scale (VAS) also improved after treatment with dupilumab [58]. In addition, dupilumab treatment significantly improved sinus opacification as determined by the LMK score [55,59]. Regarding patients with CRS with or without comorbid asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD), or previous sinus surgery history, the majority can improve in terms of SNOT-22 and ED-5Q scores with dupilumab treatment [56,60,61]. Their need for sinonasal surgery and oral corticosteroids also decreased [62]. Dupilumab is a typical type 2 biomarker receptor antibody that decreases cytokine concentrations. The expression levels of eotaxin-3 and total IgE in nasal secretions and ECP, eotaxin-2, and eotaxin-3 in nasal tissues significantly decreased after treatment with dupilumab [63]. The level of blood eosinophils did not interact with the treatment outcomes, which means that the efficacy of dupilumab was not affected by the eosinophilic status [64]. A recent study suggested that the expression of osteoprotegerin in the serum may serve as a predictor of the clinical outcome of dupilumab treatment [65].