Endotoxin activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system

Cytokines play a critical role in the cascade of events that cause septic shok. One regulatory system suggested to be important in controlling inflammatory response is the neuroendocrine axis. One of the chemokines is cytokine induced neutrophil chemoattractant (CINC), which was first described as an immuno-modulator of peripheral tissue in inflammatory responses. To assess further the contribution of the chemokine to the central nervous system, we performed immunohistochemistry on rat brains and found strong CINC-like immunoreactivity in the posterior pituitary gland. Treatment with bacterial endotoxin (lipopolysaccharide; LPS) markedly enhanced CINC-like immunoreactivity in the posterior pituitary. Before the LPS challenge, signal for CINC mRNA was undetectable in the paraventricular hypothalamic nucleus (PVN). The LPS challenge induced strong hybridization signals of CINC mRNA in the parvocellular and magnocellular subdivision of the PVN within 15 minutes (min) and peaked at 30 min. The LPS challenge provoked no observable change in the supraoptic nucleus. These studies demonstrate the presence of an endotoxin-sensitive chemokinergic neuronal pathway in the hypothalamo-neurohypophysial system and this newly-described pathway will provide a novel information to understand another possible neuralimmune mechanism.