EXPRESSION OF INTERLEUKIN 1α AND β, AND INTERLEUKIN 1 RECEPTOR ANTAGONIST mRNA IN THE RAT CENTRAL NERVOUS SYSTEM AFTER PERIPHERAL ADMINISTRATION OF LIPOPOLYSACCHARIDES

Abstract

Interleukin 1α (IL-1α) and IL-1β, and the endogenous IL-1 receptor antagonist (IL-1ra) are known members of the IL-1 family. Using in situ hybridization histochemistry we demonstrated that following endotoxin injection (lipopolysaccharides, LPS, 2.0mg/kg, i.p.) a time dependent expression and partly different expression patterns of the cytokines occurred within the rat brain and pituitary gland. All cytokines were observed in the choroid plexus. In addition, IL-1ra mRNA expressing cells were observed scattered in the brain parenchyma, whereas scattered IL-1β mRNA expressing cells were restricted to central thalamic nuclei, the dorsal hypothalamus, and cortical regions, such as the parietal and frontal cortex. A strong IL-1β mRNA expression was found in the circumventricular organs. In the pituitary gland, a low IL-1α and a high IL-1β mRNA expression was observed, with the highest density of cytokine-expressing cells seen in the posterior pituitary. The cell types expressing the mRNA's of IL-1α, IL-1β and IL-1ra were identified as monocytes in the circumventricular organs and the pituitary gland, and as microglia in the brain parenchyma. In conclusion, the present findings revealed that cytokine production in response to a peripheral endotoxin challenge mainly occurs in peripherally derived monocytes in the circumventricular organs and the pituitary gland. IL-1β is the predominant form expressed, whereas the expression of IL-1α mRNA and IL-1ra mRNA is lower. Our observations support the view that peripherally derived IL-1 may play a role in the induction of centrally mediated illness symptoms.