Macrophage-Assisted Inflammation and Pharmacological Regulation of the Cholinergic Anti-Inflammatory Pathway

Abstract

Macrophages play an important role in the immune system. They also participate in multiple processes including angiogenesis and triggering of inflammation. The present study summarizes pieces of knowledge on the importance of macrophages in disease, especially the inflammation. Special attention is paid to the cholinergic anti-inflammatory pathway (CAP) associated with the nicotinic acetylcholine receptor (nAChR) and the parasympathetic nervous system. The current pharmacological effectiveness in suppressing the inflammation in general and the septic shock in particular, is limited. CAP was discovered recently and it seems to be a suitable target for the development of new drugs. Moreover, available drugs binding to either nAChR or acetylcholinesterase (AChE) are candidates for either an inhibition or enhancement of CAP. Though the current scientific databases do not include all necessary data on the association of CAP with body functions and the research is quite intensive, the objective of the present review is to introduce the current trends and to critically evaluate CAP and macrophage-associated pathways.

Alpha7 Nicotinic Acetylcholine Receptor Is a Target in Pharmacology and Toxicology

“…Macrophages are also a target in HIV pathology as virus can proliferate within and the pathology is also involved in macrophage mediated bystander T lymphocytes apoptosis [63]. Stimulation of the cholinergic anti-inflammatory pathway is believed to be a neuro-immunomodulatory action with fast and reliable calming of the innate immune system [64]. The cholinergic anti-inflammatory pathway was proven to be effective in sepsis treatment [65], in ischemia (myocardial ischemia reperfusion injury) [66], and rheumatoid arthritis [67].…”

“…Immunology principle of the cholinergic anti-inflammatory pathway was extensively reviewed recently [64,104]. Pharmacological stimulation of the pathway seems to be suitable for treatment of multiple diseases associated with over stimulation of immune system such as autoimmune disorders, sepsis, acute pancreatitis etc.…”

Casticin inhibits COX-2 and iNOS expression via suppression of NF-κB and MAPK signaling in lipopolysaccharide-stimulated mouse macrophages

“…Steroids and NSAIDs could significantly suppress the levels of proinflammatory cytokines, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE 2 ), and decrease the activities of the NF-κB and MAPK pathways (Pohanka et al, 2011). Clinical studies have found long-term use of NSAIDs causes increased blood pressure and gastrointestinal toxicity, and also increases vascular thrombosis and the incidence of heart failure (Uncu, 2009;Lin and Hu, 2014).…”

Electrical Vagus Nerve Stimulation Attenuates Systemic Inflammation and Improves Survival in a Rat Heatstroke Model

“…The production of pro-inflammatory cytokines derived from these cells is restricted through stimulation of α7nAChRs [33]. Huston et al [34] reported that electrical VNS failed to inhibit systemic TNF production in splenectomized mice during lethal endotoxemia, indicating that the spleen is a major contributor to the anti-inflammatory effect via the cholinergic pathway.…”