Central injection of morphine stimulates plasma corticosterone and Interleukin (IL)-6 and IL-6 R mRNAs in the pituitary and adrenals in adjuvant-induced arthritis

Adjuvant-induced arthritis (AA) in the rat is a T-cell mediated, chronic in flammatory stress in which circulating interleukin (IL)-6 levels are elevat ed. In addition, there are profound neuroendocrine changes associated with the development of hind-paw inflammation which have major implications for the ability of the rat to respond the to stress. Central injection of morphine is also able to increase circulating IL-6 concentration in control animals. In the present study we have determined the effects of a single injection of morphine into the lateral ventricle of control and AA animals on plasma corticosterone levels, on changes in plasma corticosterone and on IL-6 and IL-6 receptor mRNAs in the pituitary and adrenal gland. IL-6 and IL-6 recep tor mRNAs were increased in the anterior pituitary of AA rats given moprhin e compared with saline-treated AA rats. In the adrenal cortex, IL-6 mRNA wa s unlatered and IL-6 receptor mRNA was significantly decreased under these same conditions. AA rats were unable to mount corticosterone response to ac ute stress but were able to respond to acute stimulation with e.g. LPS. In the present study we found a sustained increase in plasma corticosterone in control animals which was still significantly elevated 2 hours following m orphine injection,with a further significant increase in AA rats. These dat a suggest that alternative systems distinct from those activated in respons e to acute stress are activated by morphine in the AA animals. The similari ty with the sustained increase in corticosterone following LPS injection su ggest that either similar pathways are involved, or that central opiates ma y be involved in mediating HPA axis response to stress.