Central monoamine and plasma corticosterone changes induced by a bacterialendotoxin: sensitization and cross-sensitization effects

Low doses of lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), or exposure to a stressor (restraint) incre ased plasma corticosterone levels. In animals pretreated with lipopolysacch aride, a marked sensitization of the corticosterone response was evident up on subsequent exposure to lipopolysaccharide, TNF-alpha, or restraint, 1 da y later. As well, the sickness-inducing effects of lipopolysaccharide, TNF- alpha and IL-1 beta were markedly increased in mice pretreated with lipopol ysaccharide. The sensitization effects were marked when the second treatmen t was administered 1 day after lipopolysaccharide administration, but not w hen a 28-day interval elapsed. In a second experiment, TNF-alpha influenced monoamine functioning in the paraventricular nucleus of the hypothalamus a nd within extrahypothalamic regions, including the central amygdala, locus coeruleus, prefrontal cortex. Moreover, serotonin activity within the centr al amygdala, as well as dopamine activity within the prefrontal cortex, wer e subject to a sensitization effect in animals pretreated with lipopolysacc haride 1 day earlier. Macrophage depletion by a suspension of clodronate li posomes attenuated the plasma corticosterone changes induced by TNF-alpha, but did not affect the sensitization. In contrast, the acute effects of TNF -alpha on central neurotransmitters were unaffected by the liposome suspens ion, but this treatment prevented the sensitization. These data may be rele vant to clinical situations in which individuals exposed to bacterial infec tions may be rendered more susceptible to the behavioural and neurochemical effects of subsequently encountered stressors and immunological challenges .