The Selective α7 Agonist GTS-21 Attenuates Cytokine Production in Human Whole Blood and Human Monocytes Activated by Ligands for TLR2, TLR3, TLR4, TLR9, and RAGE

The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia

“…et al, 1997) also decreased LPS-induced TNF-α release. This is in line with previous reports of anti-inflammatory actions of GTS-21 in the peripheral immune system (Kox et al, 2009(Kox et al, , 2011Rosas-Ballina et al, 2009). It should be noted that GTS-21 has a higher affinity for α4β2* nAChRs, on which it functions as an antagonist, than the α7 nAChR (Briggs et al, 1997).…”

“…They further suggest that the previously reported anti-inflammatory actions of nicotine on cultured microglia (Shytle et al, 2004;De Simone et al, 2005;Suzuki et al, 2006) and of GTS-21 on blood monocytes (Rosas-Ballina et al, 2009;Khan et al, 2012) are not due to classical activation of α7 nAChRs, i.e. activation leading to ion flux through the receptor.…”

Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection

“…GTS-21 is capable of reducing TNF and HMGB1 release [114,115], as well as LPS-induced NFkB activation [116]. In fact, GTS-21 attenuated TNF in endotoxin-stimulated whole blood from severe sepsis patients [117]. Nevertheless, no significant differences were found between GTS-21 and placebo-treated groups in subjects administered with LPS endotoxin [118,119].…”

Psychophysiological biomarkers explaining the association between depression and prognosis in coronary artery patients: A critical review of the literature

“…Peripheral pro-inflammatory cytokines induce activation of afferent neurons of the vagus nerve and central areas activating this nerve. The other way round the cholinergic-anti-inflammatory pathway was found to influence cytokine production of macrophages (Rosas-Ballina et al, 2009). Moreover, in a clinical study HVR was inversely correlated with inflammatory markers in both healthy individuals and CAD patients (Haensel et al, 2008) suggesting a role of the cholinergic-anti-inflammatory pathway in the pathophysiology of CAD.…”