Intragraft expression of IL-10 messenger RNA: a novel correlate of renal allograft rejection.
A major conceptual advance is the formulation that type I cytokines (such as IL-2 and IFN-gamma) enhance cellular immunity and are host-protective, and that type II cytokines (such as IL-4 and IL-10) dampen cellular immunity and facilitate the progression of infection. We have explored the intragraft expression of type I and type II cytokines during human renal allograft rejection. RNA was isolated from 98 allograft biopsies, and reverse transcription-PCR was used to amplify and identify intragraft expression of mRNA encoding IL-2, IFN-gamma, IL-4, or IL-10. Intragraft expression of IL-7 mRNA and TGF-beta 1 mRNA was also investigated. Our investigation demonstrated that: (a) intragraft expression of IL-10 mRNA and IL-2 mRNA are significant correlates of acute rejection; (b) IL-4, IL-7, IFN-gamma and TGF-beta 1 mRNA expression do not correlate with acute rejection; and (c) IL-10 does not prevent in vivo expression of IFN-gamma, IL-2, IL-7, or TGF-beta 1. Our studies identify, for the first time, a significant association between intragraft IL-10 mRNA expression and acute rejection, and suggest that treatment strategies capable of constraining IL-10 expression might be of value in the prevention of acute rejection.
Rogosin Institute, Department of Transplantation Medicine and Extracorporeal Therapy, New York Hospital-Cornell Medical Center, New York, USA.
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Sharma
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Li
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Bologa
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Li
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Mouradian
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Wang
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Serur
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Rao
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Stenzel
D001483:Base Sequence; D001706:Biopsy; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*
D007375:Interleukin-1; D007376:Interleukin-2; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma