Bonaccorso Stefania, Marino Valentina, Puzella Antonella, Pasquini Massimo, Biondi Massimo, Artini Marco, Almerighi Cristiana, Verkerk Robert, Meltzer Herbert, Maes Michael
Psychiatric Hospital, University La Sapienza, Rome, Italy.
J Clin Psychopharmacol. 2002 Feb;22(1):86-90. doi: 10.1097/00004714-200202000-00014.
There is now evidence that repeated administration of interferon-alpha (IFN-alpha) to patients with chronic active hepatitis and cancers induces depressive symptoms. There is also evidence that induction of the cytokine network modulates the serotonergic system and that major depression is related to activation of the cytokine network and disturbances in the serotonergic metabolism. The aims of this study were to examine the effects of IFN-alpha-based immunotherapy on the development of depressive symptoms in relation to its effects on plasma tryptophan and kynurenine and serum serotonin (5-HT). Eighteen patients affected by chronic active hepatitis C were treated with IFN-alpha (3-6 million units subcutaneously three to six times a week for 6 months) and had measurements of the previous parameters before starting immunotherapy and 2, 4, 16, and 24 weeks later. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Anxiety (HAM-A) scale, respectively. Immunochemotherapy with IFN-alpha (1) significantly increased the MADRS and HAM-A scores and serum kynurenine concentrations and (2) significantly reduced plasma tryptophan and serum 5-HT concentrations. IFN-alpha-based immunotherapy significantly increased the kynurenine per tryptophan quotient, which estimates the activity of indoleamine 2,3-dioxygenase, the major tryptophan-catabolizing enzyme, which is induced by IFNs. There are significant relationships between the IFN-alpha-induced changes in the MADRS score and serum kynurenine (positive) and 5-HT (negative) concentrations. Immunotherapy with IFN-alpha significantly increases the severity of depressive symptoms. The latter is related to changes in the serotonergic system, such as depletion of serum 5-HT and induction of the catabolism of tryptophan to kynurenine. It is suggested that the IFN-alpha-induced changes in the serotonergic turnover could play a role in the development of IFN-alpha-induced depressive symptoms.
目前有证据表明，对慢性活动性肝炎和癌症患者反复给予α干扰素（IFN-α）会诱发抑郁症状。也有证据表明，细胞因子网络的诱导会调节血清素能系统，且重度抑郁症与细胞因子网络的激活及血清素能代谢紊乱有关。本研究的目的是探讨基于IFN-α的免疫疗法对抑郁症状发展的影响，及其对血浆色氨酸、犬尿氨酸和血清血清素（5-HT）的影响。18例慢性丙型活动性肝炎患者接受IFN-α治疗（皮下注射300 - 600万单位，每周3至6次，共6个月），并在开始免疫治疗前及治疗后2周、4周、16周和24周测量上述各项参数。分别用蒙哥马利-阿斯伯格抑郁评定量表（MADRS）和汉密尔顿焦虑评定量表（HAM-A）测量抑郁和焦虑的严重程度。IFN-α免疫化疗（1）显著提高了MADRS和HAM-A评分以及血清犬尿氨酸浓度，（2）显著降低了血浆色氨酸和血清5-HT浓度。基于IFN-α的免疫疗法显著提高了色氨酸犬尿氨酸比值，该比值可评估吲哚胺2,3-双加氧酶的活性，吲哚胺2,3-双加氧酶是主要的色氨酸分解代谢酶，可由IFN诱导产生。IFN-α诱导的MADRS评分变化与血清犬尿氨酸（正相关）和5-HT（负相关）浓度之间存在显著相关性。IFN-α免疫疗法显著增加了抑郁症状的严重程度。后者与血清素能系统的变化有关，如血清5-HT的消耗以及色氨酸向犬尿氨酸分解代谢的诱导。提示IFN-α诱导的血清素能周转变化可能在IFN-α诱导的抑郁症状发展中起作用。
