ArticleWorld journal of gastroenterology2009
Immunotherapy for nonalcoholic steatohepatitis using the multiple cytokine production modulator Y-40138.
Article in World journal of gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- IL-23/IL-17 Axis in Chronic Hepatitis C and Non-Alcoholic Steatohepatitis-New Insight into Immunohepatotoxicity of Different Chronic Liver Diseases.International journal of molecular sciences · 2023Article
- Disease Progression and Pharmacological Intervention in a Nutrient-Deficient Rat Model of Nonalcoholic Steatohepatitis.Digestive diseases and sciences · 2019Article
- An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis.International journal of experimental pathology · 2013Article
- Innate immune reactivity of the ileum-liver axis in nonalcoholic steatohepatitis.Digestive diseases and sciences · 2012Article
- Radiation damage and radioprotectants: new concepts in the era of molecular medicine.The British journal of radiology · 2012Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the possible use of the multiple cytokine production modulator, Y-40138, as a novel immunotherapy in the rat nonalcoholic steatohepatitis (NASH) model.
methodsWe allocated 6-wk-old male F344 rats to choline-supplemented, L-amino acid-defined (CSAA) diet (control group), CSAA diet + Y-40138 (control + Y-40138 group), choline-deficient, L-amino acid-defined (CDAA) diet (NASH group), or CDAA diet + Y-40138 (NASH + Y-40138 group). In each group, we measured the plasma alanine aminotransferase (ALT) levels, and the plasma and liver levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-10 (IL-10). Tissue specimens of phosphate buffered saline-perfused liver were subjected to hematoxylin and eosin staining, Azan staining, Sirius red staining, and immunohistochemical staining (for Kupffer cells and TNF-alpha). We then extracted Kupffer cells from the collagenase-perfused livers using the Percoll gradient centrifugation method, and measured the TNF-alpha levels in the supernatant (in vitro TNF-alpha production by Kupffer cells) using an enzyme-linked immunosorbent assay kit.
resultsIn comparison to the NASH group, serum ALT elevation was mild, production of serum and liver TNF-alpha and IFN-gamma was inhibited, and IL-10 production was increased in the NASH + Y-40138 group. Amelioration of liver histology was also noted in the NASH + Y-40138 group. Kupffer cell immunohistochemical staining revealed no differences between groups, whereas TNF-alpha immunohistochemical staining showed fewer stained cells in the NASH + Y-40138 group than in the NASH group. The TNF-alpha levels in the in-vitro Kupffer cell culture supernatant were lower in the NASH + Y-40138 group than in the NASH group.
conclusionAdministration of Y-40138 to NASH model rats reduced hepatic inflammation and suppressed fibrosis. These results indicate that the multiple cytokine production modulator, Y-40138, is promising as a novel treatment for NASH.
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