A mutant protein of human interleukin-1 beta with immunostimulatory but not pyrogenic potency

Abstract

Interleukin-1 (IL-1) mediates a variety of immune and inflammatory responses. In order to understand the mechanisms involved in multiple biological functions, it is important to define the active sites of IL-1. Using the technique for site-specific mutagenesis, we tested whether the arginine residue at the 4th position in human IL-1 beta is essential for multiple biological activities. In our experiments, the fourth position is replaced by a non-basic amino acid--either glycine or aspartic acid. The resulting mutant protein shows both immunostimulatory activity and the ability to induce hematopoietic growth factors similar to native IL-1 beta, but has a markedly reduced pyrogenic potency. Therefore, the mutant protein of IL-1 beta may represent a good candidate for use in vivo as an adjuvant for poor immunogenic vaccines.