Interleukin-6 deficiency fails to prevent chronic rejection after aortic allografts in apolipoprotein E-deficient mice.
BACKGROUND
Chronic vascular rejection (CVR) is characterized by an intimal thickening in the arteries of allografts due to immunoinflammatory reactions and smooth muscle cell proliferation. Interleukin 6 (IL-6) levels are increased in patients with graft rejection, however the role of IL-6 in CVR is not known. We investigated if IL-6 deficiency in the recipient could prevent CVR after an aortic allograft.


METHODS
Donor aortas from wild-type DBA/2 mice were transplanted into C57BL/6 recipients, either wild-type mice or mice deficient for IL-6 (IL-6(-/-)), apolipoprotein E (ApoE(-/-)), or both (IL-6(-/-)ApoE(-/-)). Alloantibody titers were determined at Day 30, 60, or 90 after grafting. The grafts were examined for CVR lesions by morphometry and immunohistology.


RESULTS
All recipient allografts displayed lesions typical for CVR. The lesions were larger in IL-6-deficient strains, and significantly so in IL-6(-/-)ApoE(-/-) recipients. Early immunoglobulin (Ig) G1 alloantibody deposits were observed in the grafts of ApoE-deficient strains and late IgG2a deposits in the grafts of IL-6-deficient strains. A rapid and sustained type 1 helper T cell (Th1; IgG2a) alloresponse in IL-6(-/-) mice, and a strong type 2 helper T cell (Th2; IgG1) response in ApoE(-/-) mice were observed. IL-6(-/-)ApoE(-/-) mice displayed the highest alloantibody titer, with a Th1 dominance.


CONCLUSIONS
Unexpectedly, IL-6 deficiency in the recipient mice did not prevent CVR lesions but even aggravated them in IL-6(-/-)ApoE(-/-) recipients. This was associated with increased local and systemic alloresponses.
Yacoub-Youssef
Houda
H
Institut National de la Santé et de la Recherche Médicale (Inserm), U858, I2MR, Toulouse, France.
Blaes
Nelly
N
Calise
Denis
D
Thiers
Jean Claude
JC
Therville
Nicole
N
Benoist
Hervé
H
Ségui
Bruno
B
Al Saati
Talal
T
Thomsen
Mogens
M
D000818:Animals; D001011:Aorta / Q000637:transplantation*; D001057:Apolipoproteins E / Q000172:deficiency*; D006084:Graft Rejection / Q000276:immunology*; D015850:Interleukin-6 / Q000172:deficiency*; D007518:Isoantibodies / Q000097:blood; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D014184:Transplantation, Homologous / Q000276:immunology*; D014655:Vascular Resistance / Q000276:immunology
D001057:Apolipoproteins E; D015850:Interleukin-6; D007518:Isoantibodies