Chronic morphine potentiates the inflammatory response by disrupting interleukin-1beta modulation of the hypothalamic-pituitary-adrenal axis.
Interleukin-1-beta (IL-1beta) 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-1beta-induction of corticotropin releasing factor (CRF) mRNA and plasma corticosterone levels. Leukocyte-endothelial adhesion (LEA) in rat mesenteric venules increased during IL-1beta- and FMLP-induced inflammation. Chronic morphine potentiated the LEA response to either IL-1beta or FMLP alone, and greatly enhanced LEA in response to combined IL-1beta and FMLP. Thus, it appears that chronic morphine exposure may promote a potentially damaging inflammatory reaction by disrupting the balance between IL-1beta-mediated local inflammation and the anti-inflammatory effects of the HPA axis.
House
S D
SD
Department of Biology, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA.
Mao
X
X
Wu
G
G
Espinelli
D
D
Li
W X
WX
Chang
S L
SL
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005246:Feedback / Q000187:drug effects / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D008643:Mesentery / Q000098:blood supply / Q000166:cytology; D009020:Morphine / Q000008:administration & dosage*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014699:Venules / Q000166:cytology / Q000187:drug effects
D007375:Interleukin-1; D012333:RNA, Messenger; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009020:Morphine; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone