Arce A, Castrillón P O, Della Maggiore V, Cardinali D P, Esquifino A I
Departmento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Madrid, España.
Biol Signals. 1996 Nov-Dec;5(6):334-42. doi: 10.1159/000109206.
This work was undertaken to analyze the interrelationships between prolactin and cyclosporine in affecting immune responsiveness in submaxillary lymph nodes. Male rats received an anterior pituitary graft within breast muscles on day 5, or under the kidney capsule, on day 30 or 60 of life. On day 70 (rats operated on day 5 or 30) or on day 100 (rats operated on day 60) animals were injected with Freund's complete adjuvant and cyclosporine (5 mg/kg for 5 days), and were killed 2 days after immunization. Natural killer (NK) activity in submaxillary lymph node decreased in neonatally pituitary-grafted rats and increased in rats grafted on day 30 or 60, as did lymph node cellularity. Lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced proliferation diminished in lymph nodes of rats grafted on day 30 or 60, respectively. Cyclosporine treatment diminished lymph node cell number and NK activity and increased the proliferative response to ConA. Cyclosporine depressive effect on lymph node cellularity was counteracted by the presence of a pituitary graft, as were the inhibition of NK activity and the stimulatory effect on ConA-induced cell proliferation. In pituitary-grafted rats, cyclosporine decreased submaxillary lymph node LPS-induced proliferation. Cyclosporine decreased the high circulating prolactin levels found in pituitary-grafted rats. The results are compatible with age-dependent, inhibitory and promoting activities of hyperprolactinemia on immune responses in lymph nodes, affected in a complex antagonistic and synergistic way by cyclosporine immunosuppression.
本研究旨在分析催乳素与环孢素在影响颌下淋巴结免疫反应性方面的相互关系。雄性大鼠在出生后第5天于胸肌内植入垂体前叶移植物,或在出生后第30天或60天于肾被膜下植入。在出生后第70天(出生后第5天或30天接受手术的大鼠)或第100天(出生后第60天接受手术的大鼠),给动物注射弗氏完全佐剂和环孢素(5mg/kg,连续给药5天),并在免疫后2天处死。颌下淋巴结中的自然杀伤(NK)活性在新生期接受垂体移植的大鼠中降低,而在出生后第30天或60天接受移植的大鼠中升高;淋巴结细胞数量也呈现同样的变化。在出生后第30天或60天接受移植的大鼠的淋巴结中,脂多糖(LPS)和伴刀豆球蛋白A(ConA)诱导的增殖分别减少。环孢素处理可减少淋巴结细胞数量并降低NK活性,同时增加对ConA的增殖反应。垂体移植物的存在可抵消环孢素对淋巴结细胞数量的抑制作用,对NK活性的抑制作用以及对ConA诱导的细胞增殖的刺激作用也同样得以抵消。在接受垂体移植的大鼠中,环孢素可降低颌下淋巴结LPS诱导的增殖。环孢素可降低在接受垂体移植的大鼠中所发现的高循环催乳素水平。这些结果表明,高催乳素血症对淋巴结免疫反应具有年龄依赖性的抑制和促进作用,且环孢素免疫抑制作用以复杂的拮抗和协同方式对其产生影响。