A mutant protein of human interleukin-1 beta with immunostimulatory but not pyrogenic potency.
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.
Nakai
S
S
Cellular Technology Institute, Otsuka Pharmaceutical Co., Ltdd., Tokushima, Japan.
Kawai
K
K
Hirai
Y
Y
Tasaka
K
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011749:Pyrogens; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D007376:Interleukin-2; D011749:Pyrogens