Jackson J C, Cross R J, Walker R F, Markesbery W R, Brooks W H, Roszman T L
Immunology. 1985 Mar;54(3):505-12.
The present study investigates the influence of pharmacological agents known to regulate biosynthesis of the neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) on the primary antibody response to sheep red blood cells (SRBC) in the CBA mouse. Systemic administration of 5-HT (4-100 mg/kg) or its precursor, 5-hydroxytryptophan (5-HTP, 50-400 mg/kg), 30-60 min before immunization resulted in dose-dependent suppression of both the IgM and IgG plaque-forming cell (PFC) response to SRBC. Conversely, para-chlorophenylalanine (PCPA, 250 mg/kg), which inhibits the rate-limiting enzyme (tryptophan hydroxylase) in 5-HT biosynthesis, markedly enhanced IgM and IgG antibody production when injected 48 hr prior to antigen. Effects of these drugs on immune processes appeared independent of observed changes in plasma corticosterone levels. Further, immune function was preserved following selective depletion of brain serotonin through intracisternal injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) in mice pretreated with desmethylimipramine (DMI). Thus, immunomodulation by serotonin appears to be mediated via peripheral mechanism(s).
本研究调查了已知调节神经递质5-羟色胺(5-羟色胺,5-HT)生物合成的药物制剂对CBA小鼠针对绵羊红细胞(SRBC)的初次抗体反应的影响。在免疫前30 - 60分钟全身给予5-HT(4 - 100毫克/千克)或其前体5-羟色氨酸(5-HTP,50 - 400毫克/千克),导致对SRBC的IgM和IgG空斑形成细胞(PFC)反应呈剂量依赖性抑制。相反,对氯苯丙氨酸(PCPA,250毫克/千克),它抑制5-HT生物合成中的限速酶(色氨酸羟化酶),在抗原注射前48小时注射时,显著增强了IgM和IgG抗体的产生。这些药物对免疫过程的影响似乎与血浆皮质酮水平的观察变化无关。此外,在预先用去甲丙咪嗪(DMI)处理的小鼠中,通过脑池内注射神经毒素5,7-二羟基色胺(5,7-DHT)选择性耗尽脑5-羟色胺后,免疫功能得以保留。因此,5-羟色胺的免疫调节作用似乎是通过外周机制介导的。