Immunomodulatory activity of oligopeptides related to interleukin 1 receptor antagonist sequence.

We examined the immunomodulatory properties of peptides from interleukin 1 receptor antagonist (IL-1Ra) with regard to the humoral (plaqueforming cells-PFC) and cellular (delayed type hypersensitivity-DTH) immune response and GvH reaction. It was found that peptide RKSSK (II) from the N-terminal part of IL-1Ra, although inactive with regard to the inhibition of IL-1-IL-1 receptor interaction, reduces immune response in a manner similar to cyclosporin A (DTH, PFC in vivo). Peptide GRKSSK (III) was even more potent, whereas peptides from respective fragment of mouse IL-1Ra were weaker immunosuppressants than II. Peptide VTKFYF (VII) from the C-terminal part of IL-1Ra, very active as IL-1 inhibitor, and its analog VIII with Asp residue, characteristic for IL-1, instead of Lys from IL-1Ra, showed only limited activity despite the previously observed competition with IL-1 for the cellular receptor. Thus, no correlation between the inhibitory and immunomodulatory properties of peptides derived from IL-1Ra was observed.