Morphine withdrawal sensitizes mice to lipopolysaccharide: elevated TNF-alpha and nitric oxide with decreased IL-12.
Mice made dependent on morphine using slow-release morphine pellets for 96 h were withdrawn by removal of pellets, followed by a sublethal dose of LPS 24 h later. These animals exhibited 100% lethality. Animals withdrawn from placebo pellets receiving LPS all survived, as did morphine-withdrawn mice receiving saline. Morphine-withdrawn LPS-treated animals had elevated serum TNF-alpha and nitric oxide levels, and depressed IL-12 levels compared to controls. Anti-TNF-alpha antibody given prior to LPS challenge afforded significant protection to morphine-withdrawn animals. These studies show that morphine withdrawal sensitizes to LPS lethality via increased production of TNF-alpha.
Feng
Pu
P
Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Meissler
Joseph J
JJ
Adler
Martin W
MW
Eisenstein
Toby K
TK
D000818:Animals; D000906:Antibodies / Q000502:physiology; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D018664:Interleukin-12 / Q000097:blood* / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008809:Mice, Inbred C3H; D009020:Morphine / Q000009:adverse effects*; D009569:Nitric Oxide / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000209:etiology*; D016019:Survival Analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; D009020:Morphine