I've sent a bug report to apple, but my guess is that this is an indexing problem
If I have 1 item unopen in the inbox it shows that there are No unopen e-mails. If I open the last remaining unopen one then it displays this large number 4294967295 as the number of unopen items
I've seen this sort of thing before back in my days as a developer (usually when you try to access a non existent element of an array of some sort or go beyond it's bounds in some way).
The only problem is I can't see how to really clear out the mailbox. Deleting it, re-booting and then re-entering it does not really clear down the data so I think I'm still left with what's in the data cache.
I guess "Erase All Content and Settings" would do it, but I'm really not keen on doing yet another full re-set.
May live with it until 4.2, see if they come up with a fix, if not try a full restore.
Any ideas?