Chronic morphine potentiates the inflammatory response by disrupting interleukin-1β modulation of the hypothalamic-pituitary-adrenal axis

Interleukin-1-beta (IL-1 beta) can promote inflammation by up-regulating vascular adhesion molecules and inhibit inflammation by activating the hypothalamic-pituitary-adrenal (HPA) axis to produce anti-inflammatory glucocorticoids. In this study, chronic morphine was shown to suppress IL-1 beta -induction of corticotropin releasing factor (CRF) mRNA and plasma corticosterone levels. Leukocyte-endothelial adhesion (LEA) in rat mesenteric venules increased during IL-1 beta- and FMLP-induced inflammation. Chronic morphine potentiated the LEA response to either IL-1 beta or FMLP alone. and greatly enhanced LEA in response to combined IL-1 beta and FMLP. Thus, it appears that chronic morphine exposure may promote a potentially damaging inflammatory reaction by disrupting the balance between IL-1 beta -mediated local inflammation and the anti-inflammatory effects of the HPA axis. (C) 2001 Elsevier Science B.V. All rights reserved.