Endocrine Abstracts

The long-term effects of an acute stress on subsequent HPA axis activity are well established. We have investigated the effects of different acute stressors on HPA activity, and the severity of inflammation in the rat model of adjuvant-induced arthritis (AA). A single injection of LPS administered to neonates can protect these rats from developing inflammation in response to adjuvant injection as adults. Similarly, LPS given to adults 3 weeks prior to adjuvant injection can prevent the onset of AA. However, although prior injection of LPS in adults one week before adjuvant injection does reduce the severity of inflammation in the AA model it is not fully protective. These data suggest major changes in susceptibility to inflammation in response to acute immune activation that take a number of weeks to become apparent.

In order to elucidate the mechanism underlying the long-term protective effect of LPS we have determined cytokine responses to LPS (derived from S. enteriditis) one and three weeks following a prior injection of LPS derived from E. coli. Responses of the pro-inflammatory cytokines IL-6, TNF-alpha and IFN-gamma to the second LPS injection were attenuated in rats pretreated with LPS one week previously compared to saline pre-injected controls. In contrast, the response of the anti-inflammatory cytokine IL-10 was unaffected by pretreatment. Similar cytokine patterns of release were observed in animals pre-injected with LPS 3 weeks prior to the second injection. HPA axis activity was elevated 3 weeks following the first LPS injection but after one week HPA axis activity was attenuated. These data suggest that LPS can afford long-term protection against inflammation by switching cytokine responsiveness towards an overall anti-inflammatory profile. The HPA axis response appears biphasic and may reflect the change in susceptibility to AA by adding to the anti-inflammatory cytokine and hormonal milieu 3 weeks after LPS.