1.2 - LXA4 and viral infections
Shirey and colleagues found that during Respiratory Syncytial Virus
(RSV) infection, macrophages from 5-LO or 15-LO knockout mice failed to
develop an alternatively activated phenotypic profile (AA-Mϕ) bothin vitro and in vivo . Furthermore, 5-LO and 15-LO mice
showed increased perivasculitis in the lungs when compared to their
wild-type counterparts. Pharmacological inhibition of lipoxygenases in
peritoneal-derived macrophages also inhibited AA-Mϕ differentiation
(Shirey et al., 2014). In addition, infant patients co-infected with RSV
and Mycoplasma pneumoniae showed lower LXA4/LTB4 ratios,
indicating that LXA4 production may be affected during co-infection (Wu
et al., 2016). Taken together, these studies suggest that LXA4 plays a
role in the alternative activation of macrophages during RSV infection
and subsequent resolution of lung pathology.
The role of LXA4 during Influenza infection is somewhat controversial.
Morita and colleagues demonstrated that LXA4 treatment during H1N1
infection in mice did not affect survival or alter levels of chemokines
(Morita et al., 2013). In contrast, the inhibition of lipoxin production
was associated with increased lethality rates in H5N1-infected mice
(Cilloniz et al., 2010). These studies suggest that the role of LXA4 may
vary depending on the viral strain.
Since the beginning of the COVID-19 pandemic, a wide range of review
articles have suggested the potential therapeutic use of bioactive
lipids and SPMs in the context of COVID-19 (see, for example, Batiha et
al., 2022; Lee, 2021). However, there is currently limited available
data on the topic. One study found a marked increase in LXA4 levels in
the BAL fluid of COVID-19 patients when compared to healthy volunteers
(Archambault et al., 2021). However, we have not found any studies that
evaluated the effect of these lipids in experimental SARS-CoV-2
infection or COVID-19. Therefore, the role of LXA4 during SARS-CoV-2
infection remains unclear.