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The intragraft cytokine mRNA pattern reflects the efficacy of steroid antirejection therapy
C C Baan1, H G Niesters, A H Balk
1Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands.
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.
Insights
Methylprednisolone antirejection therapy effectively downregulates intragraft cytokine mRNA expression in cardiac allograft recipients. Successful treatment correlates with reduced interleukin-2 and interleukin-4 mRNA levels, indicating therapy efficacy.
Area of Science:
- Immunology
- Molecular Biology
- Transplantation Medicine
Background:
- Investigating the impact of antirejection therapy on intragraft cytokine mRNA expression is crucial for understanding treatment efficacy in organ transplantation.
- Cardiac allograft recipients are susceptible to rejection, necessitating effective immunosuppressive strategies.
Purpose of the Study:
- To determine the effect of methylprednisolone antirejection therapy on intragraft cytokine mRNA expression in cardiac allograft recipients.
- To correlate intragraft cytokine mRNA profiles with the sensitivity or resistance to methylprednisolone treatment.
Main Methods:
- Cardiac allograft recipients received three doses of intravenous methylprednisolone (1 gm each) as antirejection therapy.
- Endomyocardial biopsy specimens were analyzed for intragraft mRNA expression of immunoregulatory (interleukin-2, interleukin-4) and inflammatory cytokines (interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha) and the interleukin-2 receptor (p55 chain) using reverse-transcriptase polymerase chain reaction.
Main Results:
- Pretreatment biopsy specimens showed constitutive expression of several cytokine mRNAs, with no clear differentiation between methylprednisolone-sensitive and -resistant rejections.
- Successful antirejection therapy led to overall downregulation of intragraft cytokine mRNA expression.
- Posttreatment, methylprednisolone-sensitive rejections showed significantly lower interleukin-2 (0% vs. 88%, p = 0.005) and interleukin-4/interleukin-6 (17% vs. 88%, p = 0.03) mRNA expression compared to resistant rejections.
Conclusions:
- Intragraft cytokine mRNA profiles reflect the efficacy of methylprednisolone antirejection therapy in cardiac allograft recipients.
- Monitoring specific cytokine mRNA levels, such as interleukin-2, may serve as a biomarker for treatment response.