The present invention provides genes of the viral genus leporipox that encode immunomodulatory proteins. The present invention also provides therapeutic compositions containing these polypeptides and methods for use for treating a variety of inflammatory and autoimmune disorders. In one preferred embodiment, the present invention provides methods for producing the immunomodulatory polypeptides in a substantially pure form. In another preferred embodiment, the invention provides methods for treating individuals diagnosed with autoimmune or inflammatory disorders by gene therapy. In yet another preferred embodiment, the methods and compositions of the present invention may be used to treat cancer. Finally, the invention provides methods to identify and isolate additional leporipox virus immunomodulatory polypeptides.