OBJECTIVE: To assess nitric oxide (NO) production and different displays of NO synthase (NOS) isoforms in patients with Kawasaki disease (KD) before and after intravenous immunoglobulin (IVIG) treatment. STUDY DESIGN: Blood and urine samples were collected from patients with KD before IVIG treatment and 3 days afterward. Age-matched febrile patients with various diseases served as control patients. Plasma NOx (NO3- + NO2-) levels were measured as NO production. Real-time reverse transcriptase-polymerase chain reaction and immunohistochemical staining were used to detect differential NOS isoform expression in mononuclear leukocytes (MNCs). RESULTS: Patients with KD (n = 40) had higher levels of NOx than the non-KD febrile control patients. The elevated NOx levels in patients with KD were significantly associated with the occurrence of coronary artery dilation (>3 mm). These elevated NOx levels significantly decreased after IVIG treatment (157.8 +/- 15.9 micromol/L vs 57.0 +/- 4.27 micromol/L, P <.01). However, excretion of urinary NOx levels was not changed after IVIG treatment. Inducible but not constitutive NOS mRNA and protein in MNCs were prominently expressed but significantly decreased after IVIG treatment. CONCLUSIONS: IVIG may suppress iNOS expression of MNCs in patients with KD, thus decreasing NO-mediated inflammatory responses and coronary artery dilation.
OBJECTIVE: To assess nitric oxide (NO) production and different displays of NO synthase (NOS) isoforms in patients with Kawasaki disease (KD) before and after intravenous immunoglobulin (IVIG) treatment. STUDY DESIGN: Blood and urine samples were collected from patients with KD before IVIG treatment and 3 days afterward. Age-matched febrile patients with various diseases served as control patients. Plasma NOx (NO3- + NO2-) levels were measured as NO production. Real-time reverse transcriptase-polymerase chain reaction and immunohistochemical staining were used to detect differential NOS isoform expression in mononuclear leukocytes (MNCs). RESULTS:Patients with KD (n = 40) had higher levels of NOx than the non-KD febrile control patients. The elevated NOx levels in patients with KD were significantly associated with the occurrence of coronary artery dilation (>3 mm). These elevated NOx levels significantly decreased after IVIG treatment (157.8 +/- 15.9 micromol/L vs 57.0 +/- 4.27 micromol/L, P <.01). However, excretion of urinary NOx levels was not changed after IVIG treatment. Inducible but not constitutive NOS mRNA and protein in MNCs were prominently expressed but significantly decreased after IVIG treatment. CONCLUSIONS: IVIG may suppress iNOS expression of MNCs in patients with KD, thus decreasing NO-mediated inflammatory responses and coronary artery dilation.
Authors: David Burgner; Sonia Davila; Willemijn B Breunis; Sarah B Ng; Yi Li; Carine Bonnard; Ling Ling; Victoria J Wright; Anbupalam Thalamuthu; Miranda Odam; Chisato Shimizu; Jane C Burns; Michael Levin; Taco W Kuijpers; Martin L Hibberd Journal: PLoS Genet Date: 2009-01-09 Impact factor: 5.917