Oxidative tryptophan metabolism in renal allograft recipients: Increased kynurenine synthesis is associated with inflammation and OKT3 therapy
| Autor: | Edward W. Bermes, Kenneth D. Thompson, Parvathy M. Russell, Gordon J. Kinzler, Craig R. Reckard, Earle W. Holmes, Robert C. Flanigan |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Adult
Graft Rejection Male medicine.medical_specialty Adolescent Immunology Inflammation Biology Biochemistry Muromonab-CD3 Pathogenesis Interferon-gamma chemistry.chemical_compound Postoperative Complications Adrenal Cortex Hormones Predictive Value of Tests Internal medicine Biopsy medicine Humans Immunology and Allergy Interferon gamma Molecular Biology Kynurenine Kidney transplantation Retrospective Studies Creatinine medicine.diagnostic_test Tryptophan Hematology Middle Aged medicine.disease Kidney Transplantation Tryptophan Oxygenase Endocrinology chemistry Virus Diseases Female medicine.symptom Gram-Negative Bacterial Infections Oxidation-Reduction Biomarkers medicine.drug |
| Zdroj: | Cytokine. 4:205-213 |
| ISSN: | 1043-4666 |
| DOI: | 10.1016/1043-4666(92)90057-x |
| Popis: | Serum concentrations of tryptophan (TRP) and kynurenine (KYN) were determined in renal allograft recipients (RAR) as an index of interferon-γ-induced, indoleamine-dioxygenase-catalysed TRP degradation. Serum TRP and KYN in RAR during periods of stable graft function were typically within the normal range, however, the median values for serum KYN demonstrated significant increases 5–7 days prior to biopsy-confirmed acute rejection (1.6-fold, P < 0.01) and on the day of biopsy (1.7-fold, P < 0.001). Serum KYN was also markedly elevated in patients who contracted viral or Gram-negative bacterial infections in the absence of graft rejection. Serum KYN was not correlated with serum creatinine in RAR nor were serum TRP or KYN affected by antirejection therapy with high dose steroids. Retrospective analysis of intra-patient changes in serum KYN demonstrated that KYN monitoring was a useful adjunct to serum creatinine in the early detection of first acute rejection episodes. The first course of OKT3 therapy was associated with low serum TRP and significant increases in serum KYN (two- to three-fold) following the first three doses. The time course of these abnormalities corresponded to that over which many of the side effects of the OKT3 ‘first dose reaction’ have been reported to occur. Significant changes in serum KYN were not observed in patients receiving repeat courses of OKT3 therapy. Significant decreases in serum TRP and significant increases in serum KYN were both prevalent and frequent in RAR during the first two postoperative months. The fact that abnormalities in oxidative TRP metabolism of a similar degree have previously been implicated in the pathogenesis of the CNS dysfunction and dementia in certain inflammatory disorders in animals and humans suggests that cytokine-induced changes in TRP and KYN could contribute to postoperative morbidity in renal transplant recipients. |
| Databáze: | OpenAIRE |
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