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Published on: September 19, 2025
Role of macrophage migration inhibitory factor in influenza H5N1 virus pneumonia
Abstract:
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.
Insights
Macrophage migration inhibitory factor (MIF) is involved in H5N1 influenza pneumonia by increasing inflammatory cytokines. Targeting MIF may offer a promising treatment strategy for H5N1 virus infections.
Area of Science:
- Immunology
- Virology
- Pathology
Background:
- H5N1 influenza causes severe, fatal pneumonia in humans and birds.
- Aberrant pulmonary inflammatory responses are implicated in H5N1 pathogenesis.
- Macrophage migration inhibitory factor (MIF) is a key regulator of innate immunity and inflammation.
Purpose of the Study:
- To investigate the role of MIF in H5N1 influenza virus pneumonia.
- To evaluate the therapeutic potential of inhibiting MIF in a murine model of H5N1 infection.
Main Methods:
- Murine model of H5N1 influenza virus infection.
- Quantification of MIF mRNA and protein levels in lungs and serum.
- Administration of isoxazolone-1 (ISO-1) to inhibit MIF action.
- Measurement of pulmonary inflammatory cytokines and chemokines.
Main Results:
- Increased MIF mRNA in lungs and MIF protein in serum of H5N1-infected mice.
- Inhibition of MIF by ISO-1 did not improve survival but significantly reduced pulmonary levels of IL-1beta, IL-6, TNF-alpha, and IP-10.
- MIF contributes to the induction of inflammatory cytokines and chemokines during H5N1 pneumonia.
Conclusions:
- MIF plays a significant role in the inflammatory response to H5N1 influenza virus.
- Targeting MIF pharmacologically may be a viable therapeutic strategy for H5N1 influenza pneumonia.
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