Characterization of anti-IL-1 alpha autoantibodies in the sera from healthy humans.
Previously, we reported that pooled normal human serum contained anti-IL-1 alpha autoantibodies. Further characterization studies have been undertaken with sera from individual healthy humans. Molecular exclusion chromatography demonstrated that 9 of 38 test sera contained anti-IL-1 alpha autoantibodies that specifically bound 125I-IL-1 alpha. The autoantibodies formed immune complexes composed of either one IgG or two IgG molecules bound to one 125I-IL-1 alpha molecule. The data suggest that the autoantibodies recognize at least two separate antigenic sites on IL-1 alpha. The autoantibodies neutralized IL-1 alpha induced IL-2 secretion by mouse thymocytes (EL-4 NOB-1). Further, in an in vitro competitive receptor binding assay, the autoantibodies completely blocked 125I-IL-1 alpha binding to recombinant human IL-1 receptor expressed on CHO cells. Our previous studies have established a correlation between inhibition of 125I-IL-1 alpha binding to receptor bearing cells and neutralization of IL-1 bioactivity in vitro and in vivo. These data suggest that development of anti-IL-1 alpha autoantibodies may play a significant role in modulating the effects of high local or systemic concentrations of IL-1 alpha.
Drug Metabolism and Pharmacokinetics, Hoffmann-La Roche Inc., Nutley, NJ 07110.
H
H
Satoh
R
R
Chizzonite
C
C
Ostrowski
G
G
Ni-Wu
H
H
Kim
B
B
Fayer
N
N
Mae
R
R
Nadeau
D J
DJ
Liberato
D000818:Animals; D001323:Autoantibodies / Q000737:chemistry* / Q000502:physiology*; D001667:Binding, Competitive; D016466:CHO Cells; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007118:Immunoassay; D007074:Immunoglobulin G / Q000145:classification; D007375:Interleukin-1 / Q000276:immunology*; D008297:Male; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001323:Autoantibodies; D007074:Immunoglobulin G; D007375:Interleukin-1; D017472:Receptors, Interleukin-1