LOCAL-ADMINISTRATION OF RECOMBINANT HUMAN INTERLEUKIN-1-BETA IN THE RAT HIPPOCAMPUS INCREASES SEROTONERGIC NEUROTRANSMISSION, HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL AXIS ACTIVITY, AND BODY-TEMPERATURE

被引:129
作者
LINTHORST, ACE
FLACHSKAMM, C
HOLSBOER, F
REUL, JMHM
机构
关键词
D O I
10.1210/en.135.2.520
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In this study, we equipped rats with a microdialysis probe in the hippocampus, which enabled stress-free intrahippocampal administration of recombinant human IL-1 beta (hIL-1 beta). Perfusion of the probes was conducted with a Ringer's solution containing 0.1 or 1.0 mu M hIL-1 beta or without hIL-1 beta, usually for 6 h. Time-dependent changes in serotonergic neurotransmission and hypothalamic-pituitaly-adrenocortical activity were simultaneously monitored by measuring serotonin [5-hydroxytryptamine (5-HT)], 5-hydroxyindoleacetic acid, and corticosterone concentrations in the dialysates. In control rats, there was a clear relationship between extracellular 5-HT concentrations in the hippocampus and behavioral activity. Extracellular 5-HT levels were up to twice as high in behaviorally active rats compared to those in resting or sleeping animals. Intrahippocampal administration of hIL-1 beta markedly increased extracellular 5-HT concentrations in the hippocampus and induced a significant decrease in behavioral activity, thereby uncoupling the parallelism between changes in 5-HT and changes in behavioral activity observed in control rats. Perfusion with 0.1 mu M hIL-1 beta, but not with 1 mu M hIL-1 beta, produced a decrease in 5-hydroxyindoleacetic acid levels, followed by a return to preinfusion levels. Moreover, intrahippocampal administration of hIL-1 beta increased hypothalamic-pituitary-adrenocortical axis activity, as evidenced by marked increases in both plasma ACTH and plasma and dialysate corticosterone levels. In addition, a rise in body temperature by approximately 2 C was observed at time points at which the effects of hIL-1 beta on 5-HT and corticosterone levels were (near-)maximal. hIL-1 beta-treated rats displayed typical characteristics of sickness behavior, such as immobility, piloerection, and a curled-up body posture, Most importantly, no effects were found either with heat-inactivated hIL-1 beta or when hIL-1 beta was administered via a probe implanted in the neocortex. Based on these results, we postulate that the hippocampal IL-1 system may play an important role in the coordination of neuroendocrine, autonomic, and behavioral responses after an immune challenge.
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页码:520 / 532
页数:13
相关论文
共 72 条
[1]   RECEPTORS FOR INTERLEUKIN-1 (ALPHA AND BETA) IN MOUSE-BRAIN - MAPPING AND NEURONAL LOCALIZATION IN HIPPOCAMPUS [J].
BAN, E ;
MILON, G ;
PRUDHOMME, N ;
FILLION, G ;
HAOUR, F .
NEUROSCIENCE, 1991, 43 (01) :21-30
[2]   INTERLEUKIN-1 BINDING-SITES ON ASTROCYTES [J].
BAN, EM ;
SARLIEVE, LL ;
HAOUR, FG .
NEUROSCIENCE, 1993, 52 (03) :725-733
[3]   REGIONAL AND CELLULAR CODISTRIBUTION OF INTERLEUKIN-1-BETA AND NERVE GROWTH-FACTOR MESSENGER-RNA IN THE ADULT-RAT BRAIN - POSSIBLE RELATIONSHIP TO THE REGULATION OF NERVE GROWTH-FACTOR SYNTHESIS [J].
BANDTLOW, CE ;
MEYER, M ;
LINDHOLM, D ;
SPRANGER, M ;
HEUMANN, R ;
THOENEN, H .
JOURNAL OF CELL BIOLOGY, 1990, 111 (04) :1701-1711
[4]   CORTICOTROPIN-RELEASING FACTOR PRODUCING NEURONS IN THE RAT ACTIVATED BY INTERLEUKIN-1 [J].
BERKENBOSCH, F ;
VANOERS, J ;
DELREY, A ;
TILDERS, F ;
BESEDOVSKY, H .
SCIENCE, 1987, 238 (4826) :524-526
[5]   IMMUNOREGULATORY FEEDBACK BETWEEN INTERLEUKIN-1 AND GLUCOCORTICOID HORMONES [J].
BESEDOVSKY, H ;
DELREY, A ;
SORKIN, E ;
DINARELLO, CA .
SCIENCE, 1986, 233 (4764) :652-654
[6]  
BESEDOVSKY HO, 1992, FRONT NEUROENDOCRIN, V13, P61
[7]   AUTONOMIC THERMOREGULATION AFTER SEPARATION OF THE PREOPTIC AREA FROM THE HYPOTHALAMUS IN RATS [J].
BLATTEIS, CM ;
BANET, M .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1986, 406 (05) :480-484
[8]   NEURAL MECHANISMS IN THE PYROGENIC AND ACUTE-PHASE RESPONSES TO INTERLEUKIN-1 [J].
BLATTEIS, CM .
INTERNATIONAL JOURNAL OF NEUROSCIENCE, 1988, 38 (1-2) :223-232
[9]  
BLATTEIS CM, 1990, YALE J BIOL MED, V63, P133
[10]  
BLATTEIS CM, 1988, FASEB J, V2, pA1531