The intragraft cytokine mRNA pattern reflects the efficacy of steroid antirejection therapy.
BACKGROUND
We studied the effect of antirejection therapy on intragraft cytokine mRNA expression.


METHODS
Therapy consisted of three doses of 1 gm of intravenous methylprednisolone. We determined its effect on intragraft mRNA expression of immunoregulatory (interleukin-2, interleukin-4) and inflammatory cytokines (interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha), and the high-affinity interleukin-2 receptor (p55 chain) in endomyocardial biopsy specimens from cardiac allograft recipients.


RESULTS
By reverse-transcriptase polymerase chain reaction methods, we detected mRNA transcription for interleukin-2 in 56% of the pretreatment endomyocardial biopsy specimens (n = 16), for interleukin-4 in 31%, and for interleukin-6 in 56% of the specimens, and interleukin-2 receptor, interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha were constitutively expressed. Individual cytokine mRNA profiles were not helpful in differentiating between rejections that proved to be methylprednisolone resistant (n = 9) or methylprednisolone sensitive (n = 7). After successful antirejection therapy, the overall intragraft mRNA expression was downregulated. None of the posttreatment endomyocardial biopsy specimens taken from six patients with methylprednisolone-sensitive rejections expressed the interleukin-2 gene, in contrast to 88% of the endomyocardial biopsy specimens obtained from eight patients with methylprednisolone-resistant rejections (p = 0.005). Moreover, intragraft interleukin-4 and interleukin-6 mRNA transcripts were hardly detectable (both 17%) in methylprednisolone-reversible rejections, but in ongoing rejections interleukin-4 mRNA expression was found in 62% (p = 0.14), and interleukin-6 was found in 88% of the endomyocardial biopsy specimens (p = 0.03). Semiquantitative analysis showed that the intragraft interleukin-2 receptor, interleukin-1 beta, and tumor necrosis factor-alpha mRNA levels were lower in posttreatment endomyocardial biopsy specimens from methylprednisolone-reversible rejections than in endomyocardial biopsy specimens from methylprednisolone-irreversible rejections (p = 0.03).


CONCLUSIONS
Our data suggest that the efficacy of antirejection therapy with methylprednisolone is reflected in intragraft cytokine mRNA profiles.
Baan
C C
CC
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Niesters
H G
HG
Balk
A H
AH
Mochtar
B
B
Zondervan
P E
PE
Weimar
W
W
D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D016207:Cytokines / Q000235:genetics*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone