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

in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology by Heba S Mehran, Soad Nady, Rami B Kassab, Omar A Ahmed-Farid, Rehab E El-Hennamy

TLDR

  • This study looked at how a protein called recombinant interleukin-22 (rIL-22) affects the gut-brain axis in mice with a parasite infection called schistosomiasis. The study found that rIL-22 reduced inflammation, oxidative damage, and neuropathological signs associated with schistosomiasis. The study also found that the efficacy of rIL-22 increased significantly when it was administered at the time of light offset. This study suggests that rIL-22 could be a useful immunotherapy for schistosomiasis in humans.

Abstract

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.

Overview

  • The study investigates the effect of recombinant interleukin-22 (rIL-22) administration at different times of the day on inflammation, oxidative status, and neurotransmitter release in the gut-brain axis of Schistosoma mansoni-infected mice. The study aims to determine the primary objective of the study, which is to investigate the efficacy of rIL-22 in reducing inflammation, oxidative damage, and neuropathological signs associated with schistosomiasis. The study uses a murine model of schistosomiasis and administers rIL-22 at the onset or offset of the light phase for 14 days. The study uses a control group, an infected group, and rIL-22 treated groups. The study measures the levels of IL-1β, TNF-α, NF-κβ, IL-22, IL-17, GSH, MDA, NO, BCL2, BDNF, and neurotransmitter release. The study aims to answer the question of whether rIL-22 administration at different times of the day has a significant effect on inflammation, oxidative status, and neurotransmitter release in the gut-brain axis of Schistosoma mansoni-infected mice.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The study identifies significant differences in the results between the control group, the infected group, and the rIL-22 treated groups. The study finds that rIL-22 administration reduced the levels of IL-1β, TNF-α, NF-κβ, and enhanced the production of IL-22 and IL-17. The treatment with IL-22 increased GSH and reduced MDA and 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. The study finds that the efficacy of IL-22 increased significantly upon its administration at the time of light offset.

Implications and Future Directions

  • The study explains the significance of the study's findings and their potential impact on the field of research or clinical practice. The study identifies limitations of the study that need to be addressed in future research. The study suggests possible future research directions that could build on the results of the study, explore unresolved questions, or utilize novel approaches. The study highlights the potential of rIL-22 as an immunotherapy for inflammation, oxidative damage, and neuropathological signs associated with schistosomiasis. The study suggests that the efficacy of IL-22 increases significantly upon its administration at the time of light offset, which could be a useful finding for future research and clinical practice. The study identifies limitations in the study, such as the use of a murine model of schistosomiasis, which may not fully represent the human condition. The study suggests future research directions, such as investigating the efficacy of rIL-22 in human subjects and exploring the long-term effects of rIL-22 administration. The study also suggests utilizing novel approaches, such as combining rIL-22 with other therapies or using rIL-22 as a preventive measure rather than a treatment.
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