Effects of monoclonal antibodies to specific epitopes of rat interleukin-1 beta (IL-1 beta) on IL-1 beta-induced ACTH, corticosterone and IL-6 responses in rats.
Recently, we developed a panel of monoclonal antibodies (MoAbs) to rat IL-1 beta and found that MoAbs binding to the aminoacid sequences 66-85 and 123-143 of mature rIL-1 beta inhibited the binding of rIL-1 beta to murine EL4 cells. Here we study whether MoAbs to these and other domains of IL-1 interfere with the biological effects of rIL-1 beta in adult male rats in vivo. Administration of rIL-1 beta (1 or 5 micrograms/kg i.v.) enhanced the plasma concentrations of ACTH, corticosterone (CORT) and of IL-6 in a time- (0.5-4 h) and dose-dependent manner. Because 2 h after 5 micrograms/kg i.v., all three parameters were consistently elevated, this dose and time interval was used for further studies. Prior to injection, rIL-1 beta was incubated alone or in the presence of a MoAb (10 mg/kg) for 30 min at 37 degrees C or at 4 degrees C. Plasma ACTH, CORT and IL-6 responses to these mixtures are compared to those obtained after preincubation of rIL-1 beta with a non-IL-1 binding MoAb (PEN7). SILK 3, a MoAb that binds to the 66-85 domain of rIL-1 beta, reduced the ACTH and IL-6 responses by 48 and 45% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Schotanus
K
K
Research Institute Neurosciences Vrije University, Faculty of Medicine, Department of Pharmacology, Amsterdam, The Netherlands.
Meloen
R H
RH
Puijk
W C
WC
Berkenbosch
F
F
Binnekade
R
R
Tilders
F J
FJ
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D003345:Corticosterone / Q000096:biosynthesis*; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D008969:Molecular Sequence Data; D010913:Pituitary-Adrenal System / Q000276:immunology; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone