Preferential localization of systemically administered radiolabeled interleukin 1alpha in experimental inflammation in mice by binding to the type II receptor.
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.
van der Laken
C J
CJ
Department of Nuclear Medicine, University Hospital Nijmegen, 6500 HB Nijmegen, The Netherlands. J.vanderLaken@Nugen.AZN.NL
Boerman
O C
OC
Oyen
W J
WJ
van de Ven
M T
MT
Chizzonite
R
R
Corstens
F H
FH
van der Meer
J W
JW
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
D007375:Interleukin-1; D007457:Iodine Radioisotopes; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins