Journal of Neuroimmunology, 39 (1992) 57-66 57 © 1992 Elsevier Science Publishers B.V. All rights reserved 0165-5728/92/$05.00 JNI 02197 Role of arachidonic acid metabolism on corticotropin-releasing factor (CRF)-release induced by interleukin-1 from superfused rat hypothalami Juan C. Cambronero, Francisco J. Rivas, Jos6 Borrell and Carmen Guaza Department of Psychobiology, Cajal Institute, CSIC, Madrid, Spain (Received 20 November 1991) (Revised, received 20 February 1992) (Accepted 20 February 1992) Key words: Interleukin-1; Corticotropin-releasing factor; Hypothalamic perifusion; Phospholipase A2; Cyclooxygenase; Prostaglandin Summary The present work shows that the corticotropin-releasing factor (CRF)-releasing activity of interleukin-1 (IL-1) is partially inhibited by a phospholipase A 2 (mepacrine) or a cyclooxygenase (indomethacin) inhibitor, but is not affected by inhibition of the lypooxygenase pathway with norhydroguaiaretic acid. These results indicate that the metabolism of arachidonic acid plays an important role as mediator of the effects of IL-1 on CRF release. It is also shown that products of the cyclooxygenase activity such as prostaglandins can stimulate CRF secretion by a direct action on the hypothalamus. Whereas PGE 2 failed to induce increases on CRF release, PGF2~ stimulated in a dose-dependent manner (21-340 nM), the CRF release from continuous perifused hypothalami. It is suggested that PGF2~ could be involved as a messenger in the hypothalamic CRF secretion induced by IL-1. Introduction There is considerable evidence indicating a bidirectional communication between the im- mune and central nervous system (Ballieux and Heijnen, 1987; Dantzer and Kelly, 1989; Ader, 1990). The hypothalamic-pituitary-adrenal (H-P- A) axis plays an important role in the relationship between the immune and neuroendocrine sys- tems (Bateman et al., 1989). The interleukins (ILs), cytokines essential for the immune re- Correspondence to: C. Guaza, Department of Psychobiology, Cajal Institute, CSIC, Doctor Arce 37, 28002 Madrid, Spain. sponse (Claman, 1987), appear to play an impor- tant role in this neur.oimmune communication. lnterleukin-1, a monokine which activates T-cell proliferation (Dinarello, 1989), has a potent acti- vating effect on the H-P-A axis, increasing plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone (Bateman et al., 1989; Dunn, 1990; Schettini, 1990). Most evidence indi- cates a hypothalamic site of IL-1 action, inducing corticotropin-releasing factor (CRF) secretion. Arachidonic acid metabolites or eicosanoids are lipid autocoids which modulate a great num- ber of cell functions in many cell types (Johnson et al., 1983). Arachidonic acid (AA) is metabo- lized by two distinct oxygenase pathways with