Recombinant Interleukin − 2 2 Immunotherapy Ameliorates Inflammation and Promotes the Release of Monoamine Neurotransmitters in the Gut-Brain Axis of Schistosoma mansoni-Infected Mice

• Published in: Journal of neuroimmune pharmacology 2024-07, Vol.19 (1), p.37, Article 37
• Main Authors: Mehran, Heba S., Nady, Soad, Kassab, Rami B., Ahmed-Farid, Omar A., El-Hennamy, Rehab E.
• Format: Article
• Language: English
• Subjects: Animals; Biogenic Monoamines - metabolism; Biomedical and Life Sciences; Biomedicine; Brain-Gut Axis - drug effects; Brain-Gut Axis - physiology; Cell Biology; Cytokines; Immunology; Immunotherapy; Immunotherapy - methods; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Interleukin-22; Interleukins - metabolism; Male; Mice; Mice, Inbred BALB C; Neurosciences; Neurotransmitter Agents - metabolism; Neurotransmitter Agents - pharmacology; Pharmacology/Toxicology; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Schistosomiasis mansoni - drug therapy; Schistosomiasis mansoni - immunology; Schistosomiasis mansoni - metabolism; Small intestine; Tumor necrosis factor-TNF; Virology
• ISSN: 1557-1904; 1557-1890; 1557-1904
• DOI: 10.1007/s11481-024-10133-x

Recombinant interleukin-22 (rIL-22) has been reported as a protective agent in murine models of diseases driven by epithelial injury. Parasites have a circadian rhythm and their sensitivity to a certain drug may vary during the day. Therefore, this work aimed to investigate the effect of rIL-22 administration at different times of the day on the inflammation, oxidative status, and neurotransmitter release in the gut-brain axis of the Schistosoma mansoni -infected mice. Sixty male BALB/c mice aged six weeks weighing 25–30 g were divided into a control group (injected intraperitoneally with PBS), mice infected with 80 ± 10 cercariae of S. mansoni (infected group) then injected intraperitoneally with PBS, and rIL-22 treated groups. rIL-22 was administrated intraperitoneally (400 ng/kg) either at the onset or offset of the light phase for 14 days. IL-22 administration reduced the levels of IL-1β, tumor necrosis factor-alpha (TNF-α), nuclear factor kappa beta (NF-κβ), and enhanced the production of IL-22 and IL-17. The treatment with IL-22 increased glutathione (GSH) and reduced malondialdehyde (MDA) and nitric oxide (NO) levels both in the ileum and brain. The B-cell lymphoma 2 (BCL2) protein level in the ileum was diminished after IL-22 administration. Brain-derived neurotrophic factor (BDNF) and neurotransmitter release (serotonin, 5HT, norepinephrine, NE, dopamine, DA, Glutamate, Glu, and -amino butyric acid, GABA) were improved by rIL-22. In conclusion, rIL-22 showed promising immunotherapy for inflammation, oxidative damage, and neuropathological signs associated with schistosomiasis. The efficacy of IL-22 increased significantly upon its administration at the time of light offset.