Introduction. A dynamic balance of pro- and anti-inflammatory cytokines is required to maintain homeostasis in the CNS. Acetylcholine has been demonstrated to participate to inflammatory response modulating synthesis and release of the main inflammatory mediators. Since aberrant immune responses occur in MS and influence disease outcome, we investigated the possible role of ACh in inflammatory phase of MS patients. Materials and methods. Fluorimetric and elisa assays were used to measure the levels of ACh, AChE and cytotokines in cerebrospinal fluid (CSF) and serum of MS patients. Results. We observed both in CSF and serum of MS patients an altered profile of cytokines typically associated to high inflammatory response. We demonstrated that cholinergic agonist CCh inhibits the production of IL-10 and stimulate IL-1 via muscarinic receptors in PBMC of MS patients. On the other hand nicotinic receptors appear to sustain the production of anti-inflammatory cytokines. Interestingly we found that MS patients have both in CSF and serum, lower levels of ACh as compared to controls, suggesting that altered production of anti-inflammatory cytokines in MS patients may be associated to decreased levels of ACh. Preliminary observations in fact have indicated that PBMC from MS patients produce in vitro lower levels of ACh compared to HD. Conclusions. Our data confirm the involvement of ACh in inflammatory responses and suggest that changes in ACh levels in MS patients may be considered as an additional pathogenetic mechanism that might contribute to exacerbate the inflammatory state of MS. This project was supported by FISM 2009 funds
Non-neuronal acetylcholine: a new modulator of immune response in multiple sclerosis patients / Reale, M.; DE ANGELIS, Federica; Capello, E.; Di Ioia, M.; De Luca, G.; Lugaresi, A.; Tata, Ada Maria. - In: CLINICAL NEUROPATHOLOGY. - ISSN 0722-5091. - STAMPA. - 30/3:(2011), pp. 141-141. (Intervento presentato al convegno joint Meeting XLVII Congress of Italian Association of Neuropathology, XXXVII congress of Italian Association for research on Brain Aging tenutosi a Genova Italy nel 19-21 May 2011).
Non-neuronal acetylcholine: a new modulator of immune response in multiple sclerosis patients
DE ANGELIS, FEDERICA;TATA, Ada Maria
2011
Abstract
Introduction. A dynamic balance of pro- and anti-inflammatory cytokines is required to maintain homeostasis in the CNS. Acetylcholine has been demonstrated to participate to inflammatory response modulating synthesis and release of the main inflammatory mediators. Since aberrant immune responses occur in MS and influence disease outcome, we investigated the possible role of ACh in inflammatory phase of MS patients. Materials and methods. Fluorimetric and elisa assays were used to measure the levels of ACh, AChE and cytotokines in cerebrospinal fluid (CSF) and serum of MS patients. Results. We observed both in CSF and serum of MS patients an altered profile of cytokines typically associated to high inflammatory response. We demonstrated that cholinergic agonist CCh inhibits the production of IL-10 and stimulate IL-1 via muscarinic receptors in PBMC of MS patients. On the other hand nicotinic receptors appear to sustain the production of anti-inflammatory cytokines. Interestingly we found that MS patients have both in CSF and serum, lower levels of ACh as compared to controls, suggesting that altered production of anti-inflammatory cytokines in MS patients may be associated to decreased levels of ACh. Preliminary observations in fact have indicated that PBMC from MS patients produce in vitro lower levels of ACh compared to HD. Conclusions. Our data confirm the involvement of ACh in inflammatory responses and suggest that changes in ACh levels in MS patients may be considered as an additional pathogenetic mechanism that might contribute to exacerbate the inflammatory state of MS. This project was supported by FISM 2009 fundsI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.