Redundancy of the cytokine network in the development of rejection after clinical heart transplantation

Abstract

We used reverse transcriptase–polymerase chain reaction analysis to study the effects of anti-rejection prophylaxis with an anti-interleukin (IL)-2 receptor (IL-2R) monoclonal antibody (BT563) on the allogeneic process by analyzing intragraft IL-2, IL-4, and IL-15 mRNA expression. Analysis showed an association between rejection and intragraft IL-2 mRNA and IL-4 mRNA transcription, whereas IL-15 was consitutively expressed: IL-2 62 % (8/13) during rejection versus 23 % (8/35) during immunological quiescence (P < 0.01); IL-4 69 % versus 23 % (P < 0.01). BT563 therapy influenced the intragraft mRNA expression of IL-2 and IL-4 but not of IL-15. In endomyocardial biopsies (EMB) showing rejection, mRNA expression of IL-2 was detectable in 40 % (2/5) during BT563 treatment versus 75 % (6/8) in the absence of BT563; for IL-4, 23 % versus 88 %, respectively. In contrast, IL-15 mRNA transcription was not affected. Quantitative analysis in rejection EMB showed comparable IL-15 mRNA levels during and after BT563 treatment. This study demonstrates that therapeutic intervention within the IL-2-dependent T-cell activation cascade does not completely prevent rejection. Other cytokines, such as IL-15, may participate in IL-2-independent rejections.