Corticosterone controls interleukin-1 beta expression and sickness behavior in the rat.

We studied the effect of corticosterone on interleukin (IL)-1 beta synthesis, body temperature, general activity, food consumption and fluid intake in rats treated with bacterial lipopolysaccharide (LPS). Radiotelemetry was used to assess body temperature and locomotor activity in combination with continuous automated recordings of feeding and drinking. This technique was developed as a novel method to identify and measure sickness behavior in rodents. The animals were (a) sham-operated, (b) adrenalectomized or (c) sham-operated and treated with corticosterone (10 mg/kg, subcutaneously). They were then intraperitoneally injected with vehicle or LPS at a dose (100 micrograms/kg) that in sham-operated rats induced fever and anorexia, reduced spontaneous activity and increased IL1-beta mRNA in spleen and adrenals as determined by Northern blot analysis. Adrenalectomized rats produced larger amounts of splenic IL-1 beta mRNA, reduced their general activity much more and developed a mild adipsia as compared with adrenal-intact animals. Administration of corticosterone 1 h before LPS lowered the splenic IL-1 beta mRNA content compared to LPS-treated adrenal-intact rats that did not receive corticosterone and inhibited fever and anorexia, whereas the glucocorticoid did not attenuate the endotoxin-induced suppression of locomotor activity. Our data suggest that during inflammatory conditions body temperature, sickness behavior and the synthesis of IL-1 beta are controlled by corticosterone. Different components of sickness behavior seem to be independently regulated and are under differential control by glucocorticoids.