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Peripheral Effects of Methionine-Enkephalin on Inflammatory Reactions and Behavior in the Rat

Vujić-Redžić V.b · Dimitrijević M.a · Stanojević S.a · Kovačević-Jovanović V.a · Miletić T.a · Radulović J.c
aImmunology Research Center ‘Branislav Janković’, and bInstitute of Chemistry, School of Medicine, Belgrade, Yugoslavia, cDepartment of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, Göttingen, Germany Neuroimmunomodulation 2000;8:70–77 (DOI:10.1159/000026455)


Methionine-enkephalin (Met-Enk) induces notable alterations in immune and central nervous system functions. The present study was conducted in order to compare peripheral and central effects of Met-Enk on nonspecific immunity, open field behavior and pain perception in the rat. The results showed that 0.2 mg/kg of Met-Enk given intraperitoneally (i.p.) increased concanavalin A (Con-A)-induced paw edema and enhanced basal and phorbol myristate acetate (PMA)-stimulated H2O2 production of peritoneal macrophages. Met-Enk-induced immunopotentiation was antagonized by anti-Met-Enk antibodies (anti-Met-Enk-Ig) and quaternary naltrexone (qNtx). Met-Enk injected i.p. produced an increase of horizontal and vertical locomotor activity in the open field that was reversed by i.p. administration of anti-Met-Enk-Ig and qNtx. The dose of 0.2 mg/kg of Met-Enk applied i.p. did not affect the number of writhes in the test of analgesia. Intracerebroventricular (i.c.v.) injection of Met-Enk, given in a dose that was previously shown to be immunostimulatory, enhanced only basal H2O2 production of peritoneal macrophages, and anti-Met-Enk-Ig antagonized this effect. Besides, i.c.v. treatment with anti-Met-Enk-Ig increased and decreased H2O2 production of peritoneal macrophages under basal and stimulated conditions, respectively. Met-Enk and anti-Met-Enk-Ig injected i.c.v. did not influence activity in the open field and pain sensitivity. Thus, the i.c.v. dose of Met-Enk that was sufficient to modulate immune functions did not influence behavior. It may be concluded that Met-Enk modulated nonspecific immune responses and open field behavior by peripheral mechanisms.

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