Onat A M, Ozçakar L, Oztürk M A, Uçar G, Ureten K, Dagli N, Kiraz S, Ertenli I, Calgüneri M
Gaziantep University Hospitals, Department of Rheumatology, Gaziantep, Turkey.
Clin Exp Rheumatol. 2007 Jul-Aug;25(4 Suppl 45):S16-20.
Familial Mediterranean fever (FMF) is the most common auto-inflammatory syndrome with exaggerated acute phase and inflammatory response. After revealing the MEFV gene mutation with the finally disturbed end product pyrin, some of the mechanisms were explained. However it is still unknown what triggers or ends these periodical attacks. Moreover, the treatment of up to 30% of the patients, that are resistant to colchicine is still a problem. In this study we investigated the role of serotonin in colchicine-resistant FMF patients.
Twenty-four FMF patients (male/female: 15/9) and 32 age- and sex-matched healthy controls (male/female: 17/15) were included into the study. Patients were subdivided into two groups. Thirteen had FMF attacks despite regular colchicine (colchicine-resistant group), other 11 had disease under control with colchicine for at least 6-months. Sampling was done both during the attack and ten days after its cessation. Plasma and platelet serotonin levels and acute phase reactants were studied in patients and controls.
Colchicine-resistant patients had plasma serotonin (5-HT) levels of 7.85 +/- 1.0 nmol/l during acute attacks which significantly reduced to the levels of 6.3 +/- 0.6 nmol/l (p < 0.001), after 10 days of acute attacks and these levels were significantly lower than those of attack-free patients' and controls' (10.7 +/- 0.2 nmol/l and 10.1 +/- 0.3 nmol/l, respectively). Platelet 5-HT level was 6.4 +/- 0.3 nmol/10(9) platelets during acute attack, and this level was increased to 9.8 +/- 0.5 nmol/10(9) platelets on the 2(nd) sampling, 10 days after the cessation of the acute attack (p < 0.001). They were both significantly higher than those of attack-free FMF patients (5.9 +/- 0.1 nmol/10(9) platelets) and healthy controls (5.7 +/- 0.3 nmol/10(9) platelets). There was a negative correlation between plasma and platelet 5-HT levels (r=-0.77, p < 0.001).
Changes in plasma and platelet 5-HT levels may be related to the disturbances in 5-HT transport mechanisms or may also be attributed to the potential role of serotonin in the inflammatory cascade. Last but not least, serotonin may have a role in the pathogenesis of FMF.
家族性地中海热(FMF)是最常见的自身炎症综合征,具有过度的急性期和炎症反应。在发现MEFV基因突变及最终受干扰的终产物吡啶后,部分机制得到了解释。然而,引发或终止这些周期性发作的因素仍不清楚。此外,高达30%对秋水仙碱耐药的患者的治疗仍是个问题。在本研究中,我们调查了血清素在对秋水仙碱耐药的FMF患者中的作用。
本研究纳入了24例FMF患者(男/女:15/9)和32例年龄及性别匹配的健康对照者(男/女:17/15)。患者被分为两组。13例患者尽管规律服用秋水仙碱仍有FMF发作(秋水仙碱耐药组),另外11例患者秋水仙碱控制病情至少6个月。在发作期及发作停止后10天进行采样。研究了患者和对照者的血浆和血小板血清素水平及急性期反应物。
秋水仙碱耐药患者在急性发作期血浆血清素(5-HT)水平为7.85±1.0 nmol/l,急性发作10天后显著降至6.3±0.6 nmol/l(p<0.001),且这些水平显著低于无发作患者和对照者(分别为10.7±0.2 nmol/l和10.1±0.3 nmol/l)。急性发作期血小板5-HT水平为6.4±0.3 nmol/10⁹血小板,急性发作停止10天后的第二次采样时该水平升至9.8±0.5 nmol/10⁹血小板(p<0.001)。它们均显著高于无发作的FMF患者(5.9±0.1 nmol/10⁹血小板)和健康对照者(5.7±0.3 nmol/10⁹血小板)。血浆和血小板5-HT水平呈负相关(r=-0.77,p<0.001)。
血浆和血小板5-HT水平的变化可能与5-HT转运机制的紊乱有关,也可能归因于血清素在炎症级联反应中的潜在作用。最后但同样重要的是,血清素可能在FMF的发病机制中起作用。