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Acute Systemic Experimental Inflammation Does Not Reduce Human Odor Identification Performance.

ABSTRACT: Olfactory dysfunction is a common symptom of various diseases, but the underlying pathophysiology has not been fully understood. Evidence from both animal and human studies suggests that local inflammation of the olfactory epithelium is linked to olfactory dysfunction. However, whether systemic inflammation causes olfactory dysfunction is yet to be determined. In the present behavioral study, we set out to test whether acute systemic inflammation impairs olfactory identification performance by inducing a transient and controlled state of systemic inflammation using an experimental endotoxemia model. We treated young healthy participants (N = 20) with a relatively high dose (2.0 ng/kg) of lipopolysaccharide (LPS) and a placebo treatment in a double-blind within-subject design, and assessed participants' ability to identify odors using the MONEX-40, a reliable method for experimental assessment of odor identification ability in healthy and young individuals. Our results show that olfactory identification performance was not affected by the acute systemic inflammation triggered by the injection of LPS. Moreover, odor identification performance following the LPS injection was not associated with levels of circulating proinflammatory cytokines (interleukin-6, interleukin-8, and tumor necrosis factor-α). Because experimental LPS-induced systemic inflammation does not affect olfactory identification performance, our findings suggest that chronic, rather than transient, systemic inflammation is a more likely mechanism to explore in order to explain the olfactory deficits observed in inflammatory diseases.

SUBMITTER: Tognetti A

PROVIDER: S-EPMC8015794 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Acute Systemic Experimental Inflammation Does Not Reduce Human Odor Identification Performance.

Tognetti Arnaud A Sarolidou Georgia G Lasselin Julie J Lekander Mats M Olsson Mats J MJ Lundström Johan N JN

Chemical senses 20210101

Olfactory dysfunction is a common symptom of various diseases, but the underlying pathophysiology has not been fully understood. Evidence from both animal and human studies suggests that local inflammation of the olfactory epithelium is linked to olfactory dysfunction. However, whether systemic inflammation causes olfactory dysfunction is yet to be determined. In the present behavioral study, we set out to test whether acute systemic inflammation impairs olfactory identification performance by i ...[more]

PMID: 33537776

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Project description:BACKGROUND & AIMS:Acute pancreatitis (AP) is characterized by severe inflammation and acinar cell death. Transmembrane protein 173 (TMEM173 or STING) is a DNA sensor adaptor protein on immune cells that recognizes cytosolic nucleic acids and transmits signals that activate production of interferons and the innate immune response. We investigated whether leukocyte STING signaling mediates inflammation in mice with AP. METHODS:We induced AP in C57BL/6J mice (control) and C57BL/6J-Tmem173gt/J mice (STING-knockout mice) by injection of cerulein or placement on choline-deficient DL-ethionine supplemented diet. In some mice, STING signaling was induced by administration of a pharmacologic agonist. AP was also induced in C57BL/6J mice with bone marrow transplants from control or STING-knockout mice and in mice with disruption of the cyclic GMP-AMP synthase (Cgas) gene. Pancreata were collected, analyzed by histology, and acini were isolated and analyzed by flow cytometry, quantitative polymerase chain reaction, immunoblots, and enzyme-linked immunosorbent assay. Bone-marrow-derived macrophages were collected from mice and tested for their ability to detect DNA from dying acinar cells in the presence and absence of deoxyribonuclease (DNaseI). RESULTS:STING signaling was activated in pancreata from mice with AP but not mice without AP. STING-knockout mice developed less severe AP (less edema, inflammation, and markers of pancreatic injury) than control mice, whereas mice given a STING agonist developed more severe AP than controls. In immune cells collected from pancreata, STING was expressed predominantly in macrophages. Levels of cGAS were increased in mice with vs without AP, and cGAS-knockout mice had decreased edema, inflammation, and other markers of pancreatic injury upon induction of AP than control mice. Wild-type mice given bone marrow transplants from STING-knockout mice had less pancreatic injury and lower serum levels of lipase and pancreatic trypsin activity following induction of AP than mice given wild-type bone marrow. DNA from dying acinar cells activated STING signaling in macrophages, which was inhibited by addition of DNaseI. CONCLUSIONS:In mice with AP, STING senses acinar cell death (by detecting DNA from dying acinar cells) and activates a signaling pathway that promotes inflammation. Macrophages express STING and activate pancreatic inflammation in AP.

Project description:BackgroundSystemic sclerosis is a multisystem inflammatory and vascular lesion leading to extensive tissue fibrosis. A reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor, DZ2002, modulates the pathologic processes of various inflammatory diseases and autoimmune diseases. This study is designed to investigate the therapeutic potentiality of DZ2002 for experimental systemic sclerosis models.MethodsThe anti-inflammatory and anti-fibrotic features of DZ2002 and its mechanisms were investigated in a bleomycin (BLM)-induced dermal fibrosis mice model. The effects of DZ2002 on expression of extracellular matrix components and TGF-? signaling in human dermal fibroblasts were analyzed. Simultaneously, the effects of DZ2002 on macrophage activation and endothelial cell adhesion molecule expression were also evaluated.ResultsDZ2002 significantly attenuated dermal fibrosis in BLM-induced mice. Consistently, DZ2002 inhibited the expression of various molecules associated with dermal fibrosis, including transforming growth factor ?1, connective tissue growth factor, tumor necrosis factor-?, interferon-?, IL-1?, IL-4, IL-6, IL-10, IL-12p40, IL-17A, and monocyte chemotactic protein 1 in the lesional skin of BLM-induced mice. Furthermore, DZ2002 decreased the proportion of macrophages, neutrophils, and T cells (especially T helper cells) in the skin tissue of BLM-induced mice. In addition, DZ2002 attenuated both M1 macrophage and M2 macrophage differentiation in vivo and in vitro. Importantly, DZ2002 directly reversed the profibrotic phenotype of transforming growth factor-?1-treated dermal fibroblasts and suppressed ICAM-1, VCAM-1, VEGF, bFGF, and ET-1 expression in endothelial cells. Finally, our investigations showed that DZ2002 relieved systemic sclerosis by regulating fibrosis TGF-?/Smad signaling pathway.ConclusionsDZ2002 prevents the development of experimental dermal fibrosis by reversing the profibrotic phenotype of various cell types and would be a potential drug for the treatment of systemic sclerosis.

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Acute Systemic Experimental Inflammation Does Not Reduce Human Odor Identification Performance.

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Acute Systemic Experimental Inflammation Does Not Reduce Human Odor Identification Performance.

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