Therapeutic JAK inhibition does not impact lung injury during viral or bacterial pneumonia in male mice
Abstract Influenza infections are often complicated by secondary bacterial infections such as MRSA pneumonia, which increase morbidity and mortality. Viral infections lead to an inflammatory response that includes elevated levels of IL‐6 and interferons. IL‐6 activates the JAK/STAT signaling pathway...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-02-01
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| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.70232 |
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| Summary: | Abstract Influenza infections are often complicated by secondary bacterial infections such as MRSA pneumonia, which increase morbidity and mortality. Viral infections lead to an inflammatory response that includes elevated levels of IL‐6 and interferons. IL‐6 activates the JAK/STAT signaling pathway, amplifying downstream inflammation. Given the clinical efficacy of the JAK inhibitor baricitinib in reducing disease severity in COVID‐19, we evaluated its impact in a murine model of influenza, MRSA, and post‐influenza MRSA pneumonia. Additionally, because IL‐6 inhibitory therapies have improved outcomes during COVID‐19, we evaluated the impact of IL‐6 deletion on post‐influenza MRSA pneumonia. In our studies, baricitinib effectively inhibited the JAK/STAT pathway in the lungs, as demonstrated by decreased interferon‐stimulated genes (ISGs) and STAT3 phosphorylation. Despite this inhibition, baricitinib did not cause a global suppression of cytokines. Notably, baricitinib treatment did not impair either antiviral or antibacterial host immunity, inflammatory cell recruitment, or lung tissue injury. IL‐6 deficiency did not alter weight loss, inflammatory cell recruitment, or bacterial burden during post‐influenza MRSA pneumonia. These findings suggest that both JAK inhibition via baricitinib and IL‐6 deletion do not enhance host defense or limit tissue injury in murine models of influenza and post‐influenza MRSA pneumonia. |
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| ISSN: | 2051-817X |