{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T15:16:25Z","timestamp":1793891785748,"version":"4.8.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2010,9,28]],"date-time":"2010-09-28T00:00:00Z","timestamp":1285632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Cite this as: P. C. Olsen, T. P. T. Ferreira, M. F. Serra, F. A. Farias\u2010Filho, B. P. Fonseca, J. P. B. Viola, R. S. B. Cordeiro, P. M. R. Silva, J. C. S. Costa and M. A. Martins, Clinical &amp; Experimental Allergy, 2011 (41) 250\u2013259.<\/jats:p><\/jats:sec><jats:sec><jats:title>Summary<\/jats:title><jats:p><jats:bold>Background\n\t\t\t\t\t<\/jats:bold> Inhalation of the local anaesthetic lidocaine has been suggested to be beneficial for asthmatics, but airway anaesthesia is unpleasant and may exacerbate bronchoconstriction. Our previous study showed that inhalation of the lidocaine analogue JMF2\u20101 can elicit the anti\u2010inflammatory properties of lidocaine without anaesthesia. This prompted further research on the mechanism of action and putative therapeutic application of JMF2\u20101.<\/jats:p><jats:p><jats:bold>Objective\n\t\t\t\t\t<\/jats:bold> We tested the hypothesis that JMF2\u20101 would prevent allergen\u2010induced lung inflammation and airway hyperresponsiveness (AHR) by modulating T cell function <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Methods\n\t\t\t\t\t<\/jats:bold> Local and systemic changes in leucocyte levels, cytokine production and lung mechanics were examined in a murine model of lung inflammation. JMF2\u20101 (0.05\u20132%) or saline was aerosolized twice a day during the ovalbumin (OVA)\u2010provocation period (19\u201321 days post\u2010sensitization). Analyses were performed 24\u2003h after the final challenge. Primary cultured lymph node cells were used to assess the effects of JMF2\u20101 (100\u2013600\u2003\u03bc<jats:sc>m<\/jats:sc>) at the cellular level.<\/jats:p><jats:p><jats:bold>Results\n\t\t\t\t\t<\/jats:bold> OVA challenge resulted in lung recruitment of CD4<jats:sup>+<\/jats:sup> T cells and eosinophils, increased generation of inflammatory cytokines and AHR to inhaled methacholine within 24\u2003h. These changes were prevented by JMF2\u20101 nebulization, and occurred in parallel with an increase in the number of apoptotic cells in the lung. JMF2\u20101 treatment did not alter levels of CD4<jats:sup>+<\/jats:sup> or CD8<jats:sup>+<\/jats:sup> T cells in the thymus or lymph nodes of na\u00efve mice, although it inhibited OVA\u2010induced IL\u201013 production and the lymphocyte proliferative response <jats:italic>in vitro<\/jats:italic>. It also induced apoptosis of OVA\u2010activated lymphocytes in a mechanism sensitive to z\u2010VAD, indicating that JMF2\u20101 mediates caspase\u2010dependent apoptosis.<\/jats:p><jats:p><jats:bold>Conclusion\n\t\t\t\t\t<\/jats:bold> Inhalation of JMF2\u20101 prevents the cardinal features of asthma by reducing T<jats:sub>H<\/jats:sub>2 cytokine generation and lung eosinophilic inflammatory infiltrates via local inhibition of T cell function and survival. JMF2\u20101 may represent a novel therapeutic alternative for asthma control with distinct advantages over local anaesthetics.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2222.2010.03580.x","type":"journal-article","created":{"date-parts":[[2010,9,28]],"date-time":"2010-09-28T09:43:18Z","timestamp":1285666998000},"page":"250-259","source":"Crossref","is-referenced-by-count":32,"title":["Lidocaine\u2010derivative JMF2\u20101 prevents ovalbumin\u2010induced airway inflammation by regulating the function and survival of T cells"],"prefix":"10.1111","volume":"41","author":[{"given":"P. C.","family":"Olsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. P. T.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. F.","family":"Serra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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