Comparison of human interleukin-1 beta and its 163-171 peptide in bone resorption and the immune response.
Human interleukin-1 beta (IL-1 beta) caused a dose- and time-dependent enhancement of the release of 45Ca from prelabeled mouse calvaria in organ culture. In addition, IL-1 beta dose-dependently stimulated the formation of prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha in the calvarial bones. However, IL-1 beta-induced 45Ca release was only partially inhibited by blocking the PGE2 response with indomethacin, suggesting that enhanced PGE2 formation in response to IL-1 beta is not necessary to obtain a bone resorptive effect, but that prostaglandins potentiate the action of IL-1 beta. The synthetic nonapeptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, administered simultaneously with antigen (SRBC) to C3H/HeN male mice, induced a dose-dependent enhancement of specific antibody-producing cells in the spleen (PFC). The degree of PFC stimulation was comparable to that caused by native human IL-1 beta. In mouse bone cultures, neither 45Ca release nor prostanoid formation was stimulated by fragment 163-171. These data indicate that (1) IL-1 beta-induced stimulation of bone resorption is dissociable from IL-1 beta-induced increase of prostanoid biosynthesis and (2) the epitope of the IL-1 beta molecule involved in the immunostimulatory effects may be different from that involved in the stimulatory effects on bone resorption.
Lerner
U H
UH
Department of Oral Pathology, University of Umeå, Sweden.
Ljunggren
O
O
Dewhirst
F E
FE
Boraschi
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005480:Flurbiprofen / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D053583:Interleukin-1beta; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D010446:Peptide Fragments; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; D011994:Recombinant Proteins; C052994:interleukin-1beta (163-171); D005480:Flurbiprofen; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium; D007213:Indomethacin