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To the Editor:The second peak (15-20 days) of the plasma NO levels in our series may be related to the major peak (3rd week) in Dr Ikemoto's series. We do not know why they did not find the first peak that occurs before IVIG therapy. The biphasic pattern is compatible with Iizaka's report1Iizuka T Oishi K Sasaki M Hatanaka Y Minatogawa Y Uemura S et al.Nitric oxide and aneurysm formation in Kawasaki disease.Acta Paediatr. 1997; 86: 470-473Crossref PubMed Scopus (21) Google Scholar that the early peak of urinary NO levels in patients with KD appears on days 4 to 6 of the illness, whereas the late peak would be found on days 15 to 17. He concluded that urinary NO levels in patients with KD peaked twice and showed an abnormally high level compared with healthy controls. The urinary NO concentration in patients with KD associated with coronary abnormalities was statistically higher than those in the patients without coronary abnormalities during the early stage of the disease, which is compatible with our findings.2Wang CL Wu YT Lee JR Liu HC Huang LT Yang KD Decrease nitric oxide (NO) production after intravenous immunoglobulin treatment in patients with Kawasaki disease.J Pediatr. 2002; 141: 560-565Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar This showed that the elevated NO levels before IVIG therapy were correlated to coronary lesions.Other studies also showed a significant increase in NO levels before IVIG treatment.3Tsukahara H Kikuchi K Matsuda M Saito M Hata I Tsuchida S et al.Endogenous nitric oxide production in Kawasaki disease.Scand J Clin Lab Invest. 1997; 57: 43-47Crossref PubMed Scopus (15) Google Scholar In our study, we showed that the decrease after the initial elevated plasma NO levels was related to the IVIG therapy and was associated with the down-regulation of inducible macrophage-type nitric oxide synthase (iNOS) expression. Whether the later peak of plasma NO levels is related to iNOS or endothelial nitric oxide synthase induction remains to be determined because both iNOS and eNOS induction in endothelial cells are implicated in the protective or offensive effects.4Kroncke KD Fehsel K Kolb-Bachofen V Inducible nitric oxide synthase in human diseases.Clin Exp Immunol. 1998; 113: 147-156Crossref PubMed Scopus (490) Google Scholar, 5Hafezi-Moghadam A Simoncini T Yang E Limbourg FP Plumier JC Rebsamen MC et al.Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase.Nat Med. 2002; 8: 473-479Crossref PubMed Scopus (461) Google Scholar Dr Ikemoto has proposed that iNOS induction, because of vascular damage, may be implicated in the later peak of plasma NO levels. However, it is unlikely that vascular damage is involved in the later elevation of NO levels because these occurred regardless of coronary lesions. Moreover, it cannot be excluded that the later elevation of plasma NO levels is related to the endogenous protective mechanism of endothelial cells from eNOS induction.5Hafezi-Moghadam A Simoncini T Yang E Limbourg FP Plumier JC Rebsamen MC et al.Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase.Nat Med. 2002; 8: 473-479Crossref PubMed Scopus (461) Google Scholar The switching of various sequential NOS isoform expressions associated with NO production may indeed be involved in the pathogenesis of the vasculitis syndrome of KD.YMPD181 To the Editor:The second peak (15-20 days) of the plasma NO levels in our series may be related to the major peak (3rd week) in Dr Ikemoto's series. We do not know why they did not find the first peak that occurs before IVIG therapy. The biphasic pattern is compatible with Iizaka's report1Iizuka T Oishi K Sasaki M Hatanaka Y Minatogawa Y Uemura S et al.Nitric oxide and aneurysm formation in Kawasaki disease.Acta Paediatr. 1997; 86: 470-473Crossref PubMed Scopus (21) Google Scholar that the early peak of urinary NO levels in patients with KD appears on days 4 to 6 of the illness, whereas the late peak would be found on days 15 to 17. He concluded that urinary NO levels in patients with KD peaked twice and showed an abnormally high level compared with healthy controls. The urinary NO concentration in patients with KD associated with coronary abnormalities was statistically higher than those in the patients without coronary abnormalities during the early stage of the disease, which is compatible with our findings.2Wang CL Wu YT Lee JR Liu HC Huang LT Yang KD Decrease nitric oxide (NO) production after intravenous immunoglobulin treatment in patients with Kawasaki disease.J Pediatr. 2002; 141: 560-565Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar This showed that the elevated NO levels before IVIG therapy were correlated to coronary lesions.Other studies also showed a significant increase in NO levels before IVIG treatment.3Tsukahara H Kikuchi K Matsuda M Saito M Hata I Tsuchida S et al.Endogenous nitric oxide production in Kawasaki disease.Scand J Clin Lab Invest. 1997; 57: 43-47Crossref PubMed Scopus (15) Google Scholar In our study, we showed that the decrease after the initial elevated plasma NO levels was related to the IVIG therapy and was associated with the down-regulation of inducible macrophage-type nitric oxide synthase (iNOS) expression. Whether the later peak of plasma NO levels is related to iNOS or endothelial nitric oxide synthase induction remains to be determined because both iNOS and eNOS induction in endothelial cells are implicated in the protective or offensive effects.4Kroncke KD Fehsel K Kolb-Bachofen V Inducible nitric oxide synthase in human diseases.Clin Exp Immunol. 1998; 113: 147-156Crossref PubMed Scopus (490) Google Scholar, 5Hafezi-Moghadam A Simoncini T Yang E Limbourg FP Plumier JC Rebsamen MC et al.Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase.Nat Med. 2002; 8: 473-479Crossref PubMed Scopus (461) Google Scholar Dr Ikemoto has proposed that iNOS induction, because of vascular damage, may be implicated in the later peak of plasma NO levels. However, it is unlikely that vascular damage is involved in the later elevation of NO levels because these occurred regardless of coronary lesions. Moreover, it cannot be excluded that the later elevation of plasma NO levels is related to the endogenous protective mechanism of endothelial cells from eNOS induction.5Hafezi-Moghadam A Simoncini T Yang E Limbourg FP Plumier JC Rebsamen MC et al.Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase.Nat Med. 2002; 8: 473-479Crossref PubMed Scopus (461) Google Scholar The switching of various sequential NOS isoform expressions associated with NO production may indeed be involved in the pathogenesis of the vasculitis syndrome of KD.YMPD181 The second peak (15-20 days) of the plasma NO levels in our series may be related to the major peak (3rd week) in Dr Ikemoto's series. We do not know why they did not find the first peak that occurs before IVIG therapy. The biphasic pattern is compatible with Iizaka's report1Iizuka T Oishi K Sasaki M Hatanaka Y Minatogawa Y Uemura S et al.Nitric oxide and aneurysm formation in Kawasaki disease.Acta Paediatr. 1997; 86: 470-473Crossref PubMed Scopus (21) Google Scholar that the early peak of urinary NO levels in patients with KD appears on days 4 to 6 of the illness, whereas the late peak would be found on days 15 to 17. He concluded that urinary NO levels in patients with KD peaked twice and showed an abnormally high level compared with healthy controls. The urinary NO concentration in patients with KD associated with coronary abnormalities was statistically higher than those in the patients without coronary abnormalities during the early stage of the disease, which is compatible with our findings.2Wang CL Wu YT Lee JR Liu HC Huang LT Yang KD Decrease nitric oxide (NO) production after intravenous immunoglobulin treatment in patients with Kawasaki disease.J Pediatr. 2002; 141: 560-565Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar This showed that the elevated NO levels before IVIG therapy were correlated to coronary lesions. Other studies also showed a significant increase in NO levels before IVIG treatment.3Tsukahara H Kikuchi K Matsuda M Saito M Hata I Tsuchida S et al.Endogenous nitric oxide production in Kawasaki disease.Scand J Clin Lab Invest. 1997; 57: 43-47Crossref PubMed Scopus (15) Google Scholar In our study, we showed that the decrease after the initial elevated plasma NO levels was related to the IVIG therapy and was associated with the down-regulation of inducible macrophage-type nitric oxide synthase (iNOS) expression. Whether the later peak of plasma NO levels is related to iNOS or endothelial nitric oxide synthase induction remains to be determined because both iNOS and eNOS induction in endothelial cells are implicated in the protective or offensive effects.4Kroncke KD Fehsel K Kolb-Bachofen V Inducible nitric oxide synthase in human diseases.Clin Exp Immunol. 1998; 113: 147-156Crossref PubMed Scopus (490) Google Scholar, 5Hafezi-Moghadam A Simoncini T Yang E Limbourg FP Plumier JC Rebsamen MC et al.Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase.Nat Med. 2002; 8: 473-479Crossref PubMed Scopus (461) Google Scholar Dr Ikemoto has proposed that iNOS induction, because of vascular damage, may be implicated in the later peak of plasma NO levels. However, it is unlikely that vascular damage is involved in the later elevation of NO levels because these occurred regardless of coronary lesions. Moreover, it cannot be excluded that the later elevation of plasma NO levels is related to the endogenous protective mechanism of endothelial cells from eNOS induction.5Hafezi-Moghadam A Simoncini T Yang E Limbourg FP Plumier JC Rebsamen MC et al.Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase.Nat Med. 2002; 8: 473-479Crossref PubMed Scopus (461) Google Scholar The switching of various sequential NOS isoform expressions associated with NO production may indeed be involved in the pathogenesis of the vasculitis syndrome of KD. YMPD181