Treating exuberant, non-resolving inflammation in the lung; Implications for acute respiratory distress syndrome and COVID-19.
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Gilroy DW, De Maeyer RPH, Tepper M, O'Brien A, Uddin M, Chen J, Goldstein DR, Akbar AN
Pharmacol Ther - (-) 107745 [2020-11-11; online 2020-11-11]
While COVID-19, the disease driven by SARS-CoV-2 has ignited interest in the host immune response to this infection, it has also highlighted the lack of treatment options for the damaging inflammatory responses driven by pathogens that precipitate the acute respiratory distress syndrome (ARDS). With the global prevalence of SARS-CoV-2 and the likelihood of a second winter spike alongside seasonal flu, the need for effective and targeted anti-inflammatory agents is even more pressing. Here we discuss the aetiology of COVID-19 and the common signalling pathways driven by SARS-CoV-2, namely p38 MAP kinase. We highlight that p38 MAP kinase becomes elevated with increasing age, thereby driving many of the inflammatory pathways that precipitate death in old people with the added drawback of impairing vaccine efficacy in this susceptible age group. Finally, we review drugs available to inhibit p38 MAP kinase, their risks-versus-benefits as well as suggested dosing regimen to combat over-exuberant innate immune responses and potentially reverse vaccine inefficacy in older patients.
PubMed 33188794
DOI 10.1016/j.pharmthera.2020.107745
Crossref 10.1016/j.pharmthera.2020.107745
pii: S0163-7258(20)30276-X
pmc: PMC7657264