Acting at the level of the brain, interleukin- (IL-)1βis considered to be one of the most potent downregulators of reproduction processes during immune/inflammatory challenge. IL-1βsuppresses gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus resulting in the inhibition of the luteinizing hormone (LH) release from the anterior pituitary (AP). However, the presence of IL-1βreceptors in the AP suggests the possible direct action of this cytokine on LH secretion. The study was designed to determine the effect of IL-1βon the LH secretion from the AP explants collected from saline and LPS-treated ewes in the follicular phase. It was found that IL-1βsuppressed () GnRH-stimulated LH release and LHβgene expression in AP explants in both groups. However, IL-1βaction was more potent in the explants collected from LPS-treated animals. Pituitaries from LPS-treated animals were characterized by increased () IL-1 type I receptor and decreased () GnRH receptor gene expression level compared to the saline-treated group. IL-1βalso affected the GnRH-R gene expression in explants collected from LPS-treated animals. Our results show that direct action of IL-1βon the pituitary gonadotropes could be one of the reasons of the reproductive processes disorders accompanying an inflammatory state.

Immune stress induced by lipopolysaccharide (LPS) influences the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) secretion. Presence of LPS interacting Toll-like receptor (TLR) 4 in the hypothalamus may enable the direct action of LPS on the GnRH/LH secretion. So, the aim of the study was to investigate the influence of intracerebroventricular (icv) injection of TLR4 antagonist on GnRH/LH secretion in anestrous ewes during LPS-induced central inflammation. Animals were divided into three groups icv-treated with: Ringer-Locke solution, LPS and TLR4 antagonist followed by LPS. It was demonstrated that TLR4 antagonist reduced LPS-dependent suppression of GnRH gene expression in the preoptic area and in the medial basal hypothalamus, and suppression of receptor for GnRH gene expression in the anterior pituitary gland. It was also shown that TLR4 antagonist reduced suppression of LH release caused by icv injection of LPS. Central administration of LPS stimulated TLR4 gene expression in the medial basal hypothalamus. It was indicated that blockade of TLR4 prevents the inhibitory effect of centrally acting LPS on the GnRH/LH secretion. This suggests that some negative effects of bacterial infection on the hypothalamic-pituitary-gonadal axis activity at the hypothalamic level may be caused by central action of LPS acting through TLR4.

The study was designed to determine the effects of peripheral injection of SB203580 on the synthesis of interleukin- (IL-) 1β, IL-6, and tumor necrosis factor (TNF)αin the hypothalamus of ewes during prolonged inflammation. Inflammation was induced by the administration of lipopolysaccharide (LPS) (400 ng/kg) over 7 days. SB203580 is a selective ATP-competitive inhibitor of the p38 mitogen-activated protein kinase (MAPK), which is involved in the regulation of proinflammatory cytokines IL-1β, IL-6 and TNFαsynthesis. Intravenous injection of SB203580 successfully inhibited (P<0.01) synthesis of IL-1βand reduced (P<0.01) the production of IL-6 in the hypothalamus. The p38 MAPK inhibitor decreased (P<0.01) gene expression of TNFαbut its effect was not observed at the level of TNFαprotein synthesis. SB203580 also reduced (P<0.01) LPS-stimulated IL-1 receptor type 1 gene expression. The conclusion that inhibition of p38 MAPK blocks LPS-induced proinflammatory cytokine synthesis seems to initiate new perspectives in the treatment of chronic inflammatory diseases also within the central nervous system. However, potential proinflammatory effects of SB203580 treatment suggest that all therapies using p38 MAPK inhibitors should be introduced very carefully with analysis of all expected and unexpected consequences of treatment.

In vertebrates, numerous processes occur in a rhythmic manner. The hormonal signal reliably reflecting the environmental light conditions is melatonin. Nocturnal melatonin secretion patterns could be disturbed in pathophysiological states, including inflammation, Alzheimer’s disease, and depression. All of these states share common elements in their aetiology, including the overexpression of interleukin- (IL-) 1βin the central nervous system. Therefore, the present study was designed to determine the effect of the central injection of exogenous IL-1βon melatonin release and on the expression of the enzymes of the melatonin biosynthetic pathway in the pineal gland of ewe. It was found that intracerebroventricular injections of IL-1β(50 µg/animal) suppressed(P<0.05)nocturnal melatonin secretion in sheep regardless of the photoperiod. This may have resulted from decreased(P<0.05)synthesis of the melatonin intermediate serotonin, which may have resulted, at least partially, from a reduced expression of tryptophan hydroxylase. IL-1βalso inhibited(P<0.05)the expression of the melatonin rhythm enzyme arylalkylamine-N-acetyltransferase and hydroxyindole-O-methyltransferase. However, the ability of IL-1βto affect the expression of these enzymes was dependent upon the photoperiod. Our study may shed new light on the role of central IL-1βin the aetiology of disruptions in melatonin secretion.

Silver nanoparticles (AgNPs) are found in open waters, but the effect of their low concentrations on an organism’s homeostasis is not fully understood. The aim of the study was to determine the short-term exposure effects of AgNPs coated by PvP (polyvinylpyrrolidone) on the homeostasis of livers and gonads in zebrafish. Sexually mature zebrafish were exposed for seven days to silver ions (0.01 mg/dm³) or AgNPs (0.01; 0.05; 0.1; 0.5; 1.0 mg/dm³). On the last day, the liver, testes, and ovaries were subjected to a histology analysis. In the liver, we analyzed the expression of the cat, gpx1a, gsr, sod1, and cyp1a genes. On the last day of the experiment, the lowest survival rate was found in the AgNPs 0.05 mg/dm³ group. The histological analysis showed that AgNPs and silver ions cause an increase in the area of hepatocytes. The highest proliferation index of hepatocytes was found in the AgNP 0.05 mg/dm³ group. Furthermore, AgNPs were found to interfere with spermatogenesis and oogonesis as well as reduce the expression levels of the cat, gpx1a, and sod1 genes in the liver compared with the control group. Based on the results, it can be concluded that exposure to AgNPs causes cytotoxic changes in zebrafish, activates the immune system, negatively affects the process of meiosis in the gonads, and generates oxidative stress.