Chronic morphine accelerates the progression of lipopolysaccharide-induced sepsis to septic shock.
Opiate addicts have been shown to have a high susceptibility to bacterial infection. We investigated how treatment with morphine alters lipopolysaccharide (LPS)-induced inflammatory responses in the rat. Chronic morphine alone elevated serum endotoxin levels. Animals treated with morphine and LPS (250 microg/kg) developed hypothermia, decreased mean arterial pressure (MAP), increased plasma thrombin anti-thrombin III (TAT) complex, and approximately 67% of animals exhibited progressive intramicrovascular coagulation. Morphine also enhanced LPS-induced leukocyte-endothelial adhesion (LEA), suppressed leukocyte flux, and corticosterone production, and elevated interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 serum levels. Our study presents both the molecular and cellular mechanisms underlying the potentiated LPS-induced inflammation and accelerated progression to septic shock seen with chronic morphine exposure.
Ocasio
Frank M
FM
Department of Biology, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA.
Jiang
Yuhui
Y
House
Steven D
SD
Chang
Sulie L
SL
D000818:Animals; D000990:Antithrombin III; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002450:Cell Communication; D003345:Corticosterone / Q000097:blood; D018450:Disease Progression; D004347:Drug Interactions; D042783:Endothelial Cells / Q000502:physiology; D004731:Endotoxins / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D008070:Lipopolysaccharides; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects; D010447:Peptide Hydrolases / Q000097:blood; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000139:chemically induced*; D012772:Shock, Septic / Q000139:chemically induced*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009294:Narcotics; D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009020:Morphine; D000990:Antithrombin III; D010447:Peptide Hydrolases; D003345:Corticosterone