Intermittent Fasting Exacerbates the Acute Immune and Behavioral Sickness Response to the Viral Mimic Poly(I:C) in Mice

Abstract

Intermitted fasting and other forms of calorie restriction are increasingly demonstrated to exert potential health benefits. Interestingly, restricted feeding is also able to mitigate sickness in response to bacterial factors stimulating Toll-like receptor 4 (TLR4). However, little is known about how fasting modifies the activity of virus-associated molecular patterns. We therefore analyzed the impact of an intermittent fasting (IF) regimen on the immune and behavioral response to the TLR3 agonist and viral mimic polyinosinic:polycytidylic acid [Poly(I:C)] in mice. The effects of intraperitoneally injected Poly(I:C) (12 mg/kg) on plasma and cerebral cytokine expression and behavior (locomotion, exploration, and ingestion) were examined in male C57BL/6N mice under control conditions and following a 9 days period of intermittent (alternate day) fasting (IF). Poly(I:C) increased the circulating levels of cytokines (TNF-α, MCP-1, IL-6, IL-10, IFN-α, IFN-γ), an effect amplified by IF. In addition, IF aggravated sickness behavior in response to Poly(I:C), while cerebral cytokine expression was enhanced by application of Poly(I:C) in the absence of a significant effect of IF. Furthermore, IF augmented the expression of neuropeptide Y (NPY) mRNA in the hypothalamus and increased the plasma levels of corticosterone, while Poly(I:C) had little effect on these readouts. Our data show that IF does not abate, but exaggerates the immune and sickness response to the viral mimic Poly(I:C). This adverse effect of IF occurs despite increased hypothalamic NPY expression and enhanced plasma corticosterone. We therefore propose that the effects of IF on the immune and behavioral responses to viral and bacterial factors are subject to different neuronal and neuroendocrine control mechanisms.

Studying the Relationship of Intermittent Fasting and β-Amyloid in Animal Model of Alzheimer’s Disease: A Scoping Review

“…This observation was further accompanied by a trend in increased anxiety-like behaviors [ 38 ]. This negative effect was also demonstrated in a poly(inosinic:cytidylic)(I:C) model of inflammation [ 50 ]. ADF was found to amplify the levels of circulating cytokines and aggravated sickness behavior in response to Poly(I:C) [ 50 ].…”

“…This negative effect was also demonstrated in a poly(inosinic:cytidylic)(I:C) model of inflammation [50]. ADF was found to amplify the levels of circulating cytokines and aggravated sickness behavior in response to Poly(I:C) [50]. Moreover, the same dietary protocol failed to demonstrate protective effects against colitis and related behavioral disorders in contrast to TRF and intermittent energy restriction (IER) [51].…”

Intermittent Fasting Aggravates Lupus Nephritis through Increasing Survival and Autophagy of Antibody Secreting Cells in MRL/lpr Mice

“…IF affects production of cytokines in several disease models [ 19 , 20 , 21 ]. In our experimental results, only IFN-γ was increased in the sera of the IF group and there was no difference in the expression of other cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, BAFF; data not shown).…”

“…In the multiple sclerosis animal model, IF decreases IFN-γ, TNF-α, and T cell proliferation [ 20 ]. However, poly(I:C)-treated mice shows increasing of circulating levels of cytokines (TNF-α, MCP-1, IL-6, IL-10, IFN-α, and IFN-γ) in IF group [ 21 ]. In lupus, several cytokines are increased (IL-6, IL-17, IFN-γ, etc.)…”

The role and its mechanism of intermittent fasting in tumors: friend or foe?

“…For example, IF in a lupus mouse model leads to the expansion of Tregs 59 . Moreover, IF can exacerbate acute immunity and behavioral sickness in response to stimulation with the viral mimic, poly(I:C) 60 . These findings suggest that the effect of a specific IF regimen on the development and function of immune cells is complex and remains to be elucidated.…”