Isolation and bioactivities of three IL-1 beta N-terminal variants.

Three distinct N-terminal variants of rhIL-1 beta can be generated by expression of the IL-1 beta gene in E. coli; the naturally occurring Ala1 species, Met0-Ala1 and des-Ala1 proteins. Since most studies with rhIL-1 beta have used a mixture of two or more variants, we have evaluated their individual bioactivities. The variants were resolved by cation exchange HPLC. Bioactivity measurement on murine thymocytes gave a potency order of Ala1 greater than des-Ala1 greater than Met0-IL-1 beta. Analysis using human T-cells co-stimulated with PMA showed a potency order of Ala1 greater than des-Ala1 greater than Met0-IL-1 beta. Thus changes in the N-terminal amino acid of IL-1 beta changes the activity of the protein. Since murine and human T-cells respond similarly, the interactions between the N-terminus of rhIL-1 beta and their receptors probably occur through comparable mechanisms.