The Cholinergic anti-inflammatory pathway (CAP) first described by Wang et al, 2003 has contemporary interest arising from the COVID-19 pandemic. While tobacco smoking has been considered an aggravating factor in the severity of COVID-19 infections, it has been suggested by some that the nicotine derived from tobacco could lessen the severity of COVID-19 infections. This spotlight briefly describes the CAP and its potential role as a therapeutic target for the treatment of COVID-19 infections using vagus nerve stimulation or selective alpha7 nicotinic acetylcholine receptor agonists.

Background and purpose: The Klotho (Klo) gene, an aging suppressor in rats, accelerates aging when disrupted and extends lifespan when overexpressed. It encodes a transmembrane protein primarily expressed in renal tubules. This study investigated the protective effects of central Klo, both alone and in combination with Cholinergic anti-inflammatory pathway (CAP) inhibition, against ischemia-reperfusion injury (IRI)-induced acute kidney injury. The current study evaluated the expression of inflammatory and antiinflammatory genes (including Il1b, Tnfa, Tgfb, Trem2, and Il10) in the kidney, alongside plasma levels of creatinine (Cr), blood urea nitrogen (BUN), and signs of acute tubular injury. Experimental approach: Klo was microinjected into the rostral ventrolateral medulla, and CAP inhibition was achieved through intraperitoneal administration of mecamylamine (Mec). Real-time RT-PCR and hematoxylin and eosin staining were used for gene expression analysis and histopathological examination, respectively. Findings/Results: The results showed elevated Cr and BUN levels, tubular injury, and increased inflammatory gene expression in IRI and IRI + Mec groups, as well as reduced Il10 in the IRI + Mec group. Klo exhibited protective effects. Elevated Tgfb expression was seen in IRI + Klo and IRI + Mec + Klo groups one week postsurgery. Conclusion and implications: These findings indicated Klo potential to extend lifespan and protect against age-related diseases, including kidney disease and inflammation, via neural modulation of peripheral immunity.