title: Preferential localization of systemically administered radiolabeled interleukin 1alpha in experimental inflammation in mice by binding to the type II receptor.
abstract: Previously, we have shown that systemically administered radiolabeled interleukin 1alpha (IL-1alpha) accumulates preferentially in inflammatory foci in mice. Since inflammation is characterized by influx of leukocytes, which represent IL-1 receptor (IL-1R) positive cells, radiolabeled IL-1 may specifically localize in inflammation by binding to its receptors on infiltrated leukocytes. This hypothesis was tested in a series of studies in mice with acute focal inflammations. Evidence for specific IL-1-IL-1R interaction in induced inflammation was found: microscopic autoradiography revealed that 125I-IL-1alpha localized at the site of inflammatory cells with time; 125I-myoglobin, a similar-sized protein with no known interactions in vivo, was not retained in the inflammation. Furthermore, the uptake 125I-IL-1alpha in inflammatory tissue was significantly lower in neutropenic mice than in immunocompetent mice (0.05+/-0.004 vs. 0.65+/-0.06% ID/g at 48 h after injection, P < 0.0007). Moreover, the uptake of 125I-IL-1alpha at the inflammatory site could be blocked with the anti-IL-1R type II antibody 4E2. At 48 h after injection, the uptake with and without blocking the type II IL-1R was 0.13+/-0.01 and 0. 65+/-0.05% ID/g, respectively (P < 0.0001). These in vivo studies provide evidence that systemically administered radiolabeled IL-1alpha localizes in inflammatory tissue by specific receptor binding, predominantly by binding to the type II IL-1R.
authors.affiliation: Department of Nuclear Medicine, University Hospital Nijmegen, 6500 HB Nijmegen, The Netherlands. J.vanderLaken@Nugen.AZN.NL
authors.forename: C J
authors.initials: CJ
authors.lastname: van der Laken
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
authors.forename: W J
authors.initials: WJ
authors.lastname: Oyen
authors.forename: M T
authors.initials: MT
authors.lastname: van de Ven
authors.forename: R
authors.initials: R
authors.lastname: Chizzonite
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism; D000818:Animals; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007249:Inflammation / Q000378:metabolism*; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D009503:Neutropenia / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013211:Staphylococcus aureus / Q000276:immunology; D013997:Time Factors
chemical_list: D007375:Interleukin-1; D007457:Iodine Radioisotopes; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins