Herman_2013_Domest.Anim.Endocrinol_44_109

The present study was designed to determine the effect of subcutaneous rivastigmine treatment on IL-1beta expression and IL-1 type I receptor (IL-1R1) gene expression in the hypothalamic structures (preoptic area [POA], anterior hypothalamus [AHA], and medial basal hypothalamus [MBH]) of ewes after lipopolysaccharide (LPS) treatment. Endotoxin treatment increased (P <= 0.01) both IL-1beta and IL-1R1 gene expression in the POA, AHA, and MBH compared with the control group, whereas concomitant rivastigmine and LPS injection abolished this stimulatory effect. It was also found that LPS elevated (P <= 0.01) IL-1beta concentration in the hypothalamus (71.0 +/- 2.3 pg/mg) compared with controls (16.1 +/- 3.6 pg/mg). The simultaneous injection of LPS and rivastigmine did not increase IL-1beta concentration in the hypothalamus (24.6 +/- 13.0 pg/mg). This central change in IL-1beta synthesis seems to be an effect of acetylcholinesterase (AChE) inhibition by rivastigmine, which decreases (P <= 0.01) the activity of this enzyme from 78.5 +/- 15.0 mumol . min(-1) . g(-1) of total protein in the control and 68.8 +/- 9.8 mumol . min(-1) . g(-1) of total protein in LPS-treated animals to 45.2 +/- 5.6 mumol . min(-1) . g(-1) of total protein in the rivastigmine and LPS-treated group. Our study showed that rivastigmine could effectively reverse the stimulatory effect of immune stress induced by LPS injection on IL-1beta synthesis through a decrease in AChE activity in the hypothalamic area of sheep. Our results also proved that the cholinergic anti-inflammatory pathway could directly modulate the central response to endotoxin.