Plasma and cerebrospinal fluid interleukin-1β during lipopolysaccharide-induced systemic inflammation in ewes implanted or not with slow-release melatonin

Abstract

Background: Interleukin-1β (IL-1β) is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cerebrospinal fluid (CSF) is peripheral circulation, while over time, cytokines produced in the brain are more important. Melatonin has been shown to decrease pro-inflammatory cytokines concentration in the brain. In ewes, melatonin is used to advance the onset of a breading season. Little is known about CSF concentration of IL-1β in ewes and its correlation with plasma during inflammation as well as melatonin action on the concentration of IL-1β in blood plasma and the CSF, and brain barriers permeability in early stage of lipopolysaccharide (LPS)-induced inflammation. Methods: Systemic inflammation was induced through LPS administration in melatonin-and sham-implanted ewes. Blood and CSF samples were collected before and after LPS administration and IL-1β and albumin concentration were measured. To assess the functions of brain barriers albumin quotient (QAlb) was used. Expression of IL-1β (Il1B) and its receptor type I (Il1r1) and type II (Il1r2) and matrix metalloproteinase (Mmp) 3 and 9 was evaluated in the choroid plexus (CP). Results: Before LPS administration, IL-1β was on the level of 62.0 ± 29.7 pg/mL and 66.4 ± 32.1 pg/mL in plasma and 26.2 ± 5.4 pg/mL and 21.3 ± 8.7 pg/mL in the CSF in sham-and melatonin-implanted group, respectively. Following LPS it increased to 159.3 ± 53.1 pg/mL and 197.8 ± 42.8 pg/mL in plasma and 129.8 ± 54.2 pg/mL and 139.6 ± 51.5 pg/mL in the CSF. No correlations was found between plasma and CSF IL-1β concentration after LPS in both groups. The QAlb calculated before LPS and 6 h after was similar in all groups. Melatonin did not affected mRNA expression of Il1B, Il1r1 and Il1r2 in the CP. The mRNA expression of Mmp3 and Mmp9 was not detected. Conclusions: The lack of correlation between plasma and CSF IL-1β concentration indicates that at the beginning of inflammation the local synthesis of IL-1β in the CP is an important source of IL-1β in the CSF. Melatonin from slow-release implants does not affect IL-1β concentration in plasma and CSF in early stage of systemic inflammation.

Melatonin enhances autophagy and decreases apoptosis induced by nanosilica in RAW264.7 cells

“…Meanwhile, we found that the levels of IL‐1β and IL‐18 might be elevated by melatonin treatment in comparison with the RAW264.7 cell group stimulated with nanosilica alone. In the early stage of systemic inflammation, the sustained release of melatonin would not affect the IL‐1β level in plasma and cerebrospinal fluid (CSF) . However, it has been reported that the exudate produced by melatonin could alter the immunosuppressive status of liver cells through the STAT3 signaling pathway, and the expression of IL‐6, IL‐10, IL‐1β, and TNF‐α produced by macrophages was reduced by hepatocellular carcinoma‐derived exosomes .…”

Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation

“…In general, the source of IL-1 β in the brain is differentiated. It may originate from (1) periphery and then is transported by brain barriers to reach the brain parenchyma or to enter the brain through the circumventricular organs [ 32 – 34 ], (2) de novo synthesis in the brain microvessel endothelium and CP [ 20 , 35 ], and (3) local synthesis in microglial and dendritic cells, astrocytes, and even neurons [ 36 ]. Therefore, it may be expected that early after LPS administration, the inhibitory action of neostigmine on central IL-1 β may result from reduction of IL-1 β able to reach the brain and from its decreased de novo synthesis in the brain microvessels endothelium (BBB) as well as CP.…”

“…It has been established that the lipid A colocalizes with CD14, TLR4, and NF κ B (translocated into the nucleus) in the choroid plexus (CP), a multifunctional organ situated at the interface between the blood and cerebrospinal fluid (CSF) [ 17 ]. In our recent studies, it was shown that activation of the LPS receptor in the CP induces mRNA expression of TLR4, CD14, and proinflammatory cytokines and their receptors and then induces cytokine secretion into the cerebrospinal fluid (CSF) [ 18 – 20 ]. Unfortunately, information about neostigmine effect on CP response to LPS challenge is lacking.…”

Photoperiod alters the choroid plexus response to LPS-induced acute inflammation in EWES

“…Indeed, the upregulation of the expression of pro-inflammatory cytokine and corresponding receptor genes was observed in the ovine ChP under LPS-challenged conditions (Kowalewska et al, 2017a;Herman et al, 2018). In ewes, the local synthesis of interleukin (IL)-1β in the ChP is an important source of IL-1β in the CSF at the onset of inflammation (Skipor et al, 2017). Centrally acting pro-inflammatory cytokines have been linked with the inhibition of gonadotropin-releasing hormone gene expression in the preoptic area (POA) in ewes during LPS-induced systemic inflammation in both anestrous during LD and the breeding season during SD .…”