mayne, keepalives might generally not create a problem. You can turn on keepalive and set it to a lower value (like 5 secs) to check this..
If you have more than 1 PC on the LAN accessing the AS400 application:
1) If there is a problem with the WAN, all PC's in the LAN will give drops.
2) If there is only one PC that is giving a drop, then there might be some problem with the specific switch port associated with it..