What is a defense for a state attempting an unconstitutional regulation of commerce of threatening letters across state lines?

Disclaimer first. I have not seen the letters and m not familiar with KY law, so my answer is specific to the constitutional question you posed assuming that the letters are indeed threatening letters meaning they threaten unlawful harm. You should consult an attorney in KY for a more definitive answer. If you are the person charged you should definitely consult an attorney in KY.

I think it is unlikely that threatening letters will be viewed as "commerce between the states." The fact that they traveled between the states does not make them commerce. I am not aware of any legitimate business whose purpose is sending threatening letters.

Even if the letters were commerce, there is nothing to stop the state from making threats of unlawful harm as unlawful as the harm itself. Every state has a some sort of statute that outlaws threatening to illegally harm someone. The fact that the threats are sent by mail from another state does not insulate the sender from liability. On the contrary, it may open them up to federal criminal prosecution as well as state prosecution.

As an example, imagine that the letters contained cocaine rather than threats, and that the cocaine was sent for the purpose of selling it. Clearly the cocaine would be commerce. KY could still prosecute because it has a legitimate state interest in keeping illegal drugs out of KY. The federal government could also prosecute under the federal drug and mail laws.