RESUMEN
AIM: Familial Mediterranean fever (FMF) is the most frequent periodic syndrome characterised by recurrent attacks of polyserositis. However, recent studies revealed that there might be an ongoing subclinical inflammation between the attacks. As nitric oxide (NO) and adrenomedullin (AM) are both synthesised in the endothelium, and mediates many functions within immune system, we considered them to be an interesting target of investigation in FMF. METHODS: Fifteen children with FMF receiving regular colchicine, ranging in age from 3 to 16 years, were investigated in comparison with 15 healthy age- and sex-matched controls. The mean age of the patients was 9.7 +/- 3.9 years. Total nitrite, a stable product of NO, was quantitated by means of the Griess reaction, while AM was measured by HPLC. RESULTS: Plasma-urinary AM and total nitrite levels were significantly higher in children with FMF. Plasma AM levels (pmol/mL) in patients and controls were 40.95 +/- 5.99 vs. 34.86 +/- 5.24, P < 0.05, and urinary AM excretion (pmol/mg creatinine) was 51.16 +/- 28.15 vs. 37.5 +/- 24.26, P < 0.05 respectively. Plasma total nitrite levels (micromol/L) in patients and controls were 44.80 +/- 10.36 vs. 32.13 +/- 9.28, P < 0.05, and urinary nitrite excretion (micromol/mg creatinine) was 2.24 +/- 1.71 vs. 1.09 +/- 0.96, P < 0.05 respectively. CONCLUSION: This study considered that AM and NO may have a role in the immuno-inflammatory process of FMF, although, whether these act to preserve, or protect against, further inflammatory injury is not clear. Our results further supports the hypothesis that these patients have subclinical inflammation between attacks.
Asunto(s)
Fiebre Mediterránea Familiar/metabolismo , Nitritos/sangre , Nitritos/orina , Péptidos/sangre , Péptidos/orina , Adolescente , Adrenomedulina , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Niño , Preescolar , Colchicina/uso terapéutico , Fiebre Mediterránea Familiar/tratamiento farmacológico , Femenino , Humanos , Masculino , Óxido Nítrico/metabolismo , Valores de ReferenciaRESUMEN
Nitric oxide (NO) is synthesized from endothelium and has an important role in the control of vascular tonus. Adrenomedullin (AM) is a potent vasodilator, and cytoprotective peptide is produced not only in adrenal medulla, but also in the vascular smooth muscle and endothelial cells. To investigate the endothelial synthesis of AM and NO, and endothelial injury in Henoch-Schönlein purpura (HSP), we measured their levels in 16 children with HSP, who were evaluated during the acute and remission phases, and compared with 12 healthy controls. Plasma AM levels (pmol/ml) were significantly higher in acute phase children (46.87+/-11.49) than in those in remission (35.59+/-12.39, p<0.01) and controls (30.70+/-9.12, p<0.001). Similarly, plasma total nitrite levels (mumol/l) were higher in acute phase patients (47.50+/-12.30) than in those in remission (35.94+/-10.08, p<0.005) and controls (34.56+/-11.51, p<0.05). Urinary excretion of AM (pmol/mg creatinine) was higher in acute phase patients (53.85+/-23.22) than in remission patients (29.97+/-9.33, p<0.01) and controls (37.43+/-15.78, p<0.05). Patients had increased urinary nitrite excretion (mumol/mg creatinine) in acute phase (2.39+/-1.18) compared to those in remission (1.53+/-0.90, p<0.05) and controls (1.05+/-0.61, p<0.005). There was no significant difference between remission phase and controls in AM and nitrite levels ( p>0.05). This study concluded that AM and NO may have a role in the immunoinflammatory process of HSP, especially in the active stage, although whether this perpetuates, or protects against, further vascular injury is not clear. Further studies are needed to clearly establish the roles of AM and NO in the pathogenesis of HSP.
Asunto(s)
Vasculitis por IgA/sangre , Nitritos/sangre , Péptidos/sangre , Adolescente , Adrenomedulina , Estudios de Casos y Controles , Niño , Femenino , Humanos , Vasculitis por IgA/fisiopatología , Vasculitis por IgA/orina , Masculino , Nitritos/orina , Péptidos/orinaRESUMEN
Henoch-Schonlein purpura (HSP) is one of the most common types of vasculitis disorders seen in childhood and is characterized by a rash, arthritis, abdominal pain, and renal involvement. Although HSP is an immunoglobulin A (IgA) related immune complex disease, the pathogenesis has not been fully elucidated. Cytokines have been implicated in the pathogenesis, but endothelins (ET) - vasoconstrictor hormones produced by endothelial cells - have not been studied in patients with HSP. In a controlled study, we measured ET-1 levels in children with HSP during the acute and remission phases. ET-1 levels were significantly higher in the HSP patients during the acute phase compared with the control group and the HSP patients in the remission phase. There was no correlation between ET-1 levels and disease severity, acute phase reactant response, or morbidity. The role of endothelins and other cytokines in the pathogenesis of HSP needs to be further explored.