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CONCLUSIONI
Il nostro studio su campioni di liquido sinoviale conferma che la NET sia estremamente espressa dai PMN in corso di artrite gottosa (MSU). Di particolare interesse è però l'osservazione che il processo sia analogo qualitativamente e quantitativamente anche alla altra principale artropatia microcristallina e cioè alla artropatia da deposito di pirofosfato di calcio (CPPD). I nostri dati morfologici e quantitativi rivelano come in effetti i PMN di liquidi sinoviali di Gotta e Condrocalcinosi vadano incontro a Netosi con conseguente produzione di abbondante NET. Questo ci fa ipotizzare che la Netosi sia un processo fisiopatologico comune nelle artriti microcristalline; è interessante anche osservare come invece nei PMN con artropatia da CPPD, in fase non infiammatoria, la NET non fosse particolarmente espressa. Recentemente è stata avanzata l’ipotesi che la NET abbia la funzione di autolimitare il meccanismo infiammatorio sostenuto da varie citochine quali la IL-1β, il TNF alfa e IL-6 in corso di attacco acuto di Gotta [68]. Questo è stato dimostrato in base ad esperimenti in vitro ed in vivo su modelli murini in cui si ipotizza che sulla NET siano presenti anche proteasi specifiche (serin-proteasi) responsabili della degradazione degli elevati contenuti di citochine pro-infiammatorie, prima fra tutte la IL-1β. I dosaggi da noi effettuati confermano un’elevata concentrazione di citochine pro-infiammatorie nei liquidi sinoviali di forme microcristalline, interessante altresì anche l’aumento di citochine anti-infiammatorie, quale la IL-10. Statisticamente non abbiamo rilevato una correlazione significativa tra i livelli di NET e la concentrazione delle varie citochine. Non possiamo escludere che data la esiguità del campione la validità statistica venga persa.
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La tipica tendenza alla autorisoluzione delle poussè artritiche in corso di artropatie microcristalline è ben nota, ma anche poco interpretabile sul piano patogenetico. Lo studio recentemente pubblicato su nature reviews, apre pertanto uno scenario affascinante negli intrensici meccanismi di malattia [69]. A riguardo se è facilmente intuibile quale possa essere il ruolo della netosi in corso di processi infettivi e cioè quello di creare una filtro extracellulare batteriotossico rimane elusivo nelle artriti microcristalline. L'ipotesi pertanto che la netosi possa essere un processo finalizzato allo spegnimento della acuzie infiammatorie indotte da microcristalli nel “milieu” articolare apre nuovi secenari nella patogenesi delle artriti microcristalline. In base ai nostri dati possiamo aggiungere che questo processo non è pertanto ristretto alla gotta ma anche alla condrocalcinosi. Limiti del nostro studio sono la ristretta casistica che è attualmente in fase di ampliamento con l'obbiettivo di valutare una possibile correlazione tra livelli di citochine pro ed anti-infiammatorie e NET.
Nel prossimo futuro, se tali dati fossero confermati, implementerebbero la conoscenza del meccanismo patogenetico delle artriti microcristalline e della loro caratteristica all’autorisoluzione durante l’attacco acuto.
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