Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy
| Autor: | C. Kablitz, R. L. Menlove, Read R. Taintor, M. P. McMurry, R. L. Baranowski, Zdenek Vavrin, James P. Kushner, John B. Hibbs, John H. Ward, Christof Westenfelder |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1992 |
| Předmět: |
Interleukin 2
Adult Male medicine.medical_specialty Arginine medicine.medical_treatment Nitric Oxide Nitric oxide Excretion chemistry.chemical_compound Interferon-gamma Nitrate Renal cell carcinoma Internal medicine medicine Humans Interferon gamma Carcinoma Renal Cell Melanoma General Medicine Middle Aged medicine.disease Kidney Neoplasms Cytokine Endocrinology Kidney Tubules chemistry Interleukin-2 Female Vascular Resistance medicine.drug Research Article |
| Popis: | An interferon-gamma, tumor necrosis factor, and interleukin-1-inducible, high-output pathway synthesizing nitric oxide (NO) from L-arginine was recently identified in rodents. High-dose interleukin-2 (IL-2) therapy is known to induce the same cytokines in patients with advanced cancer. Therefore, we examined renal cell carcinoma (RCC; n = 5) and malignant melanoma (MM; n = 7) patients for evidence of cytokine-inducible NO synthesis. Activity of this pathway was evaluated by measuring serum and urine nitrate (the stable degradation product of NO) during IL-2 therapy. IL-2 administration caused a striking increase in NO generation as reflected by serum nitrate levels (10- and 8-fold increase [P less than 0.001, P less than 0.003] for RCC and MM patients, respectively) and 24-h urinary nitrate excretion (6.5- and 9-fold increase [both P less than 0.001] for RCC and MM patients, respectively). IL-2-induced renal dysfunction made only a minor contribution to increased serum nitrate levels. Metabolic tracer studies using L-[guanidino-15N2]arginine demonstrated that the increased nitrate production was derived from a terminal guanidino nitrogen atom of L-arginine. Our results showing increased endogenous nitrate synthesis in patients receiving IL-2 demonstrate for the first time that a cytokine-inducible, high-output L-arginine/NO pathway exists in humans. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|