Interleukin 1 beta (IL-1 beta) is a potent stimulator of extracellular matrix degradation in models of osteoarthritis (OA). In contrast to bovine explant models which effectively respond to recombinant human IL-1 beta, canine models are relatively refractory to human IL-1 beta stimulation. Canine IL-1 beta cDNA was cloned in order to produce a fully potent species matched preparation of IL-1 beta for use specifically in canine models of OA. Established methods for the production of various orthologous IL-1 beta proteins from different species are problematic due to the exquisite sensitivity of the mature IL-1 beta product to N-terminal variations and the intrinsic technical challenges associated with producing an unmodified product. We have applied a seamless method of SUMO tagging and removal in order to produce a homogeneous unmodified preparation of canine IL-1 beta from Escherichia coli which was found to be a potent inducer of aggrecanase activity in isolated canine articular chondroctyes. This method combines highly efficient aspects of seamless plasmid engineering, protein purification, and precise tag removal. (c) 2006 Elsevier Inc. All rights reserved.