Role of macrophage migration inhibitory factor in influenza H5N1 virus pneumonia.
The severe and often fatal disease in humans and birds caused by H5N1 influenza viruses has been attributed to aberrant pulmonary inflammatory responses. We investigated the role of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and a pivotal regulator of innate immunity, in H5N1 influenza virus pneumonia in murine model. We found increased MIF mRNA levels in the lungs and MIF protein levels in the serum of infected mice. Although the inhibition of MIF action by isoxazolone-1 (ISO-1) did not render mice more resistant to the lethality of infection, it caused a significant reduction in pulmonary inflammatory cytokines interleukin-1 beta (IL-1beta), IL-6 and tumor necrosis factor alpha (TNF-alphalfa) and chemokine interferon-inducible protein-10 (IP-10). These results indicate the involvement of MIF in inflammatory responses to H5N1 influenza virus infections by induction of pulmonary inflammatory cytokines and chemokines, and suggest that pharmacotherapeutic approaches targeting MIF may hold promise for the treatment of H5N1 influenza virus pneumonia.
Hou
X Q
XQ
Jilin University, Changchun, PR China.
Gao
Y W
YW
Yang
S T
ST
Wang
C Y
CY
Ma
Z Y
ZY
Xia
X Z
XZ
D000818:Animals; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D019746:Intramolecular Oxidoreductases / Q000097:blood* / Q000378:metabolism; D007555:Isoxazoles / Q000008:administration & dosage; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D011024:Pneumonia, Viral / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C462499:3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester; D018925:Chemokines; D016207:Cytokines; D007555:Isoxazoles; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse