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 imm...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2005-01, Vol.174 (1), p.426-434
Main Authors: Wang, Jinghua, Barke, Roderick A, Charboneau, Richard, Roy, Sabita
Format: Article
Language:English
Subjects:
Analgesics, Opioid - pharmacology
Animals
Blotting, Western
Bronchoalveolar Lavage Fluid - immunology
Bronchoalveolar Lavage Fluid - microbiology
Chemokine CXCL2
Chemokines - metabolism
Chemotaxis, Leukocyte - drug effects
Cytokines - drug effects
Cytokines - metabolism
Disease Models, Animal
Disease Susceptibility
Galectin 3 - drug effects
Galectin 3 - metabolism
Immunity, Innate - drug effects
Lung - microbiology
Lung - pathology
Male
Mice
Morphine - pharmacology
Neutrophils - drug effects
NF-kappa B - drug effects
NF-kappa B - metabolism
Pneumococcal Infections - immunology
Receptors, Interleukin-8B - drug effects
Receptors, Interleukin-8B - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Spleen - microbiology
Streptococcus pneumoniae
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.174.1.426