Morphine impairs host innate immune response and increases susceptibility to Streptococcus pneumoniae lung infection.
Chronic morphine use impairs host innate immune response and increases susceptibility to bacteria and virus. In this study a novel mouse model of chronic morphine treatment, followed by intranasal inoculation with Streptococcus pneumoniae, was used to investigate microbial events and host innate immune response. Our results show that chronic morphine treatment markedly delayed neutrophil recruitment and increased bacterial burden in the lung, spleen, and blood with a subsequent increase in mortality. In morphine-treated animals, before neutrophil recruitment, a significant decrease in TNF-alpha, IL-1, IL-6, MIP-2, and KC was observed both in bronchoalveolar lavage fluids and in lung tissue. In the early phase of infection, we found that accumulation of galectin-3 in the alveolar space of streptococcus-infected lungs was decreased after morphine treatment. The transcription factor NF-kappaB in lung resident cells was also inhibited after morphine treatment. Taken together, these results suggest that chronic morphine treatment in an S. pneumoniae infection model suppresses NF-kappaB gene transcription in lung resident cells, which, in turn, modulates the transcriptional regulation of MIP-2 and inflammatory cytokines. The decreased synthesis of MIP-2 and inflammatory cytokines coupled with the decreased release of galectin-3 result in reduced migration of neutrophils to the site of infection, thereby increasing susceptibility to S. pneumoniae infection after morphine treatment.
Wang
Jinghua
J
Department of Pharmacology, University of Minnesota, 321 Church Street SE, Minneapolis, MN 55455, USA.
Barke
Roderick A
RA
Charboneau
Richard
R
Roy
Sabita
S
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D037502:Galectin 3 / Q000187:drug effects / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects*; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D011008:Pneumococcal Infections / Q000276:immunology*; D023063:Receptors, Interleukin-8B / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000382:microbiology
D000701:Analgesics, Opioid; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D037502:Galectin 3; D016328:NF-kappa B; D023063:Receptors, Interleukin-8B; D009020:Morphine