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 (s uch as IL-2 and IFN-gamma) enhance cellular immunity and are host-prot ective, and that type II cytokines (such as IL-4 and IL-10) dampen cel lular immunity and facilitate the progression of infection. We have ex plored the intragraft expression of type I and type II cytokines durin g human renal allograft rejection. RNA was isolated from 98 allograft biopsies, and reverse transcription-PCR was used to amplify and identi fy 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 i nvestigated. Our investigation demonstrated that: (a) intragraft expre ssion 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 intrag raft IL-10 mRNA expression and acute rejection, and suggest that treat ment strategies capable of constraining IL-10 expression might be of v alue in the prevention of acute rejection.