In Vitro Cytokine Profiles and Their Relevance to Rejection Following Renal Transplantation

Kaminski, É.; Kaminski, Anna; Bending, M. R.; Chang, Ruijie; Heads, A; Szydlo, Richard; Pereira, R. S.

doi:10.1097/00007890-199510150-00015

Cited by 32 publications

(13 citation statements)

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“…20 The influence of pretransplantation cytokine levels on rejection has been investigated in renal transplantation, with increased mean levels of interferon-␥ (IFN-␥) in the group going on to develop acute rejection. 21 However, TNF-␣ was not measured in this study. Our study suggested that TNF-␣ production less than 1,260 pg/mL predicted patients less likely to experience acute rejection.…”

Section: Discussionmentioning

confidence: 75%

Pretransplantation tumor necrosis factor-α production predicts acute rejection after liver transplantation

et al. 2000

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Immunosuppressive therapy has many adverse effects in both the short and longer term. Tailoring immunosuppression might be possible if pretransplantation parameters predicted rejection. We investigated production of the proinflammatory cytokine, tumor necrosis factor-␣ (TNF-␣), and the anti-inflammatory cytokine, interleukin-10 (IL-10), pretransplantation to determine whether there is a relation with acute rejection. Peripheral-blood mononuclear cells were obtained from patients with chronic liver disease on the waiting list for orthotopic liver transplantation and healthy controls. Cells (0.5 ؋ 10 6 ) were stimulated with 200 ng of lipopolysaccharide. Preincubation for 30 minutes with tacrolimus, cyclosporine, and dexamethasone at concentrations of 10 and 100 ng was also performed. TNF-␣ and IL-10 levels were measured by enzyme-linked immunosorbent assay. Acute rejection was defined on clinical and histological grounds. Pretransplantation in vitro production of TNF-␣ significantly (P < .05) increased in the group of patients with acute rejection (n ‫؍‬ 9) compared with those who did not develop rejection (n ‫؍‬ 12). Preincubation with dexamethasone significantly (P < .001) reduced TNF-␣ and IL-10 production in both patients and controls (n ‫؍‬ 8). IL-10 production pretransplantation was not different in those who developed acute rejection (n ‫؍‬ 9) compared with those who did not (n ‫؍‬ 9). Preincubation with tacrolimus augmented (P < .05) the production of IL-10 in patients (n ‫؍‬ 18), but not controls (n ‫؍‬ 6). Pretransplantation TNF-␣ production is increased in patients who go on to develop acute rejection posttransplantion. (Liver Transpl 2000;6:721-727.)

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Section: Discussionmentioning

confidence: 75%

Pretransplantation tumor necrosis factor-α production predicts acute rejection after liver transplantation

et al. 2000

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“…Studies show that high levels of IFN-g are evident in acutely rejecting kidneys (46). Asian populations have a higher percentage of the IFN-g low producer (A/A) genotype, as compared to the other ethnicities.…”

Section: Discussionmentioning

confidence: 99%

Ethnicity Greatly Influences Cytokine Gene Polymorphism Distribution

Hoffmann

Stanley

Cox

et al. 2002

American Journal of Transplantation

291

208

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Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytokine production and may modulate the magnitude of alloimmune responses following transplantation. Ethnicity influences allograft half-life and the incidence of acute and chronic rejection. We have questioned whether ethnic-based differences in renal allograft survival could be due in part to inheritance of cytokine polymorphisms. To address that question, we studied the inheritance patterns for polymorphisms in several cytokine genes (IL-2, IL-6, IL-10, TNF-a, TGF-b, and IFNg) within an ethnically diverse study population comprised of 216 Whites, 58 Blacks, 25 Hispanics, and 31 Asians. Polymorphisms were determined by allele-specific polymerase chain reaction and restriction fragment length analysis. We found striking differences in the distribution of cytokine polymorphisms among ethnic populations. Specifically, significant differences existed between Blacks and both Whites and Asians in the distribution of the polymorphic alleles for IL-2. Blacks, Hispanics and Asians demonstrated marked differences in the inheritance of IL-6 alleles and IL-10 genotypes that result in high expression when compared with Whites. Those of Asian descent exhibited an increase in IFN-g genotypes that result in low expression as compared to Whites. In contrast, we did not find significant ethnic-based differences in the inheritance of polymorphic alleles for TNF-a. Our results show that the inheritance of certain cytokine gene polymorphisms is strongly associated with ethnicity. These differences may contribute to the apparent influence of ethnicity on allograft outcome.

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“…Association of the gene with acute rejection and graft vascular disease after clinical heart transplantation [21]. IL2/-330T has been shown to influence the production levels of the cytokine [22].…”

Section: Methodsmentioning

confidence: 99%

Association of four DNA polymorphisms with acute rejection after kidney transplantation

Grinyó¹,

Vanrenterghem²,

Nashan³

et al. 2008

Transplant International

108

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Summary Renal transplant outcomes exhibit large inter‐individual variability, possibly on account of genetic variation in immune‐response mediators and genes influencing the pharmacodynamics/pharmacokinetics of immunosuppressants. We examined 21 polymorphisms from 10 genes in 237 de novo renal transplant recipients participating in an open‐label, multicenter study [Cyclosporine Avoidance Eliminates Serious Adverse Renal‐toxicity (CAESAR)] investigating renal function and biopsy‐proven acute rejection (BPAR) with different cyclosporine A regimens and mycophenolate mofetil. Genes were selected for their immune response and pharmacodynamic/pharmacokinetic relevance and were tested for association with BPAR. Four polymorphisms were significantly associated with BPAR. The ABCB1 2677T allele tripled the odds of developing BPAR (OR: 3.16, 95% CI [1.50–6.67]; P = 0.003), as did the presence of at least one IMPDH2 3757C allele (OR: 3.39, 95% CI [1.42–8.09]; P = 0.006). BPAR was almost fivefold more likely in patients homozygous for IL‐10 ‐592A (OR: 4.71, 95% CI [1.52–14.55]; P = 0.007) and twice as likely in patients with at least one A allele of TNF‐α G‐308A (OR: 2.18, 95% CI [1.08–4.41]; P = 0.029). There were no statistically significant interactions between polymorphisms, or the different treatment regimens. Variation in genes of immune response and pharmacodynamic/pharmacokinetic relevance may be important in understanding acute rejection after renal transplant.

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In Vitro Cytokine Profiles and Their Relevance to Rejection Following Renal Transplantation

Cited by 32 publications

References 0 publications

Pretransplantation tumor necrosis factor-α production predicts acute rejection after liver transplantation

Pretransplantation tumor necrosis factor-α production predicts acute rejection after liver transplantation

Ethnicity Greatly Influences Cytokine Gene Polymorphism Distribution

Association of four DNA polymorphisms with acute rejection after kidney transplantation

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