Skipor Janina, Kowalewska Marta, Szczepkowska Aleksandra, Majewska Anna, Misztal Tomasz, Jalynski Marek, Herman Andrzej P, Zabek Katarzyna
Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Jablonna n/Warsaw, Olsztyn, Poland.
J Anim Sci Biotechnol. 2017 Oct 1;8:76. doi: 10.1186/s40104-017-0206-0. eCollection 2017.
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.
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 ( and its receptor type I () and type II () and matrix metalloproteinase () 3 and 9 was evaluated in the choroid plexus (CP).
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 , and in the CP. The mRNA expression of and was not detected.
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.
白细胞介素-1β（IL-1β）是炎症诱导下丘脑水平生殖轴抑制的重要介质。在炎症初期，脑脊液（CSF）中细胞因子的主要来源是外周循环，而随着时间推移，脑内产生的细胞因子更为重要。褪黑素已被证明可降低脑内促炎细胞因子浓度。在母羊中，褪黑素用于提前繁殖季节的开始。关于母羊CSF中IL-1β的浓度及其在炎症期间与血浆的相关性，以及褪黑素对血浆和CSF中IL-1β浓度以及脂多糖（LPS）诱导炎症早期脑屏障通透性的作用，目前知之甚少。
通过给植入褪黑素和假植入的母羊注射LPS诱导全身炎症。在注射LPS前后采集血液和CSF样本，并测量IL-1β和白蛋白浓度。为评估脑屏障功能，使用了白蛋白商（QAlb）。在脉络丛（CP）中评估IL-1β（及其I型（）和II型（）受体以及基质金属蛋白酶（）3和9的表达。
在注射LPS前，假植入组和褪黑素植入组血浆中IL-1β水平分别为62.0±29.7 pg/mL和66.4±32.1 pg/mL，CSF中分别为26.2±5.4 pg/mL和21.3±8.7 pg/mL。注射LPS后，血浆中分别升至159.3±53.1 pg/mL和197.8±42.8 pg/mL，CSF中分别为129.8±54.2 pg/mL和139.6±51.5 pg/mL。两组注射LPS后血浆和CSF中IL-1β浓度之间均未发现相关性。所有组在注射LPS前和6小时后计算的QAlb相似。褪黑素不影响CP中、和的mRNA表达。未检测到和的mRNA表达。
血浆和CSF中IL-1β浓度缺乏相关性表明，在炎症开始时，CP中IL-1β的局部合成是CSF中IL-1β的重要来源。缓释植入物中的褪黑素在全身炎症早期不影响血浆和CSF中IL-1β的浓度。
