Artículo

Refojo, D.; Kovalovsky, D.; Young, J.I.; Rubinstein, M.; Holsboer, F.; Reul, J.M.H.M; Low, M.J.; Arzt, E. "Increased splenocyte proliferative response and cytokine production in β-endorphin-deficient mice" (2002) Journal of Neuroimmunology. 131(1-2):126-134
La versión final de este artículo es de uso interno de la institución.
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

We used β-endorphin-deficient mice as a novel approach to confirm the physiological role that opioid peptides play in the development or regulation of the immune system. We found that mice lacking β-endorphin possessed an enhanced immune response, measured in terms of splenocyte proliferation and interleukin (IL)-2 mRNA levels, in vitro production of the splenic macrophage inflammatory cytokines IL-6 and Tumor Necrosis Factor (TNF)-α and plasma IL-6 following lipopolysaccharide (LPS) administration. β-Endorphin-deficient mice had attenuated increases of plasma ACTH and corticosterone levels in response to LPS. These results are consistent with a postulated inhibitory role of endogenous β-endorphin on the immune system at multiple levels. © 2002 Elsevier Science B.V. All rights reserved.

Registro:

Documento: Artículo
Título:Increased splenocyte proliferative response and cytokine production in β-endorphin-deficient mice
Autor:Refojo, D.; Kovalovsky, D.; Young, J.I.; Rubinstein, M.; Holsboer, F.; Reul, J.M.H.M; Low, M.J.; Arzt, E.
Filiación:Laboratorio de Fisiología y Biología Molecular, Departamento de Biología, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires, Ciudad Universitaria, Pabellon II, C1428EHA Buenos Aires, Argentina
INGEBI-CONICET, Buenos Aires, Argentina
Max-Planck Institute of Psychiatry, Kraepelin str. 10, 80804 Munich, Germany
Vollum Institute, Oregon Health and Science University, Portland, OR, United States
Palabras clave:β-endorphin; Cytokines; HPA axis; Neuroimmunology; Splenocyte; beta endorphin; corticosterone; corticotropin; interleukin 12; interleukin 6; lipopolysaccharide; messenger RNA; tumor necrosis factor alpha; animal cell; animal experiment; animal model; animal tissue; article; cell proliferation; controlled study; corticosterone blood level; corticotropin blood level; cytokine production; immune response; immune system; immunoregulation; macrophage; mouse; nonhuman; priority journal; protein blood level; protein deficiency; spleen cell; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Cell Division; Cells, Cultured; Corticosterone; Cytokines; Interleukin-2; Interleukin-6; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mice, Knockout; RNA, Messenger; Spleen; Tumor Necrosis Factor-alpha
Año:2002
Volumen:131
Número:1-2
Página de inicio:126
Página de fin:134
DOI: http://dx.doi.org/10.1016/S0165-5728(02)00268-0
Título revista:Journal of Neuroimmunology
Título revista abreviado:J. Neuroimmunol.
ISSN:01655728
CODEN:JNRID
CAS:Adrenocorticotropic Hormone, 9002-60-2; beta-Endorphin, 60617-12-1; Corticosterone, 50-22-6; Cytokines; Interleukin-2; Interleukin-6; Lipopolysaccharides; RNA, Messenger; Tumor Necrosis Factor-alpha
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01655728_v131_n1-2_p126_Refojo

Referencias:

  • Alicea, C., Belkowsky, S.M., Eisenstein, T.K., Adler, M.W., Rogers, T.J., Inhibition of primary murine macrophage cytokine production in vitro following treatment with kappa-opioid agonist U50,488H (1996) J. Neuroimmunol., 64, pp. 83-90
  • Apte, R.N., Durum, S.K., Oppenheim, J.J., Opioids modulate interleukin-1 production and secretion by bone-marrow macrophages (1990) Immunol. Lett., 24, pp. 141-148
  • Arzt, E., Costas, M., Finkielman, S., Nahmod, V.E., Serotonin inhibition of tumor necrosis factor-alpha synthesis by human monocytes (1991) Life Sci., 48, pp. 2557-2562
  • Arzt, E., Stelzer, G., Renner, U., Lange, M., Müller, A., Stalla, G., Interleukin-2 and interleukin-2 receptor expression in human corticotrophic adenoma and murine pituitary cell cultures (1992) J. Clin. Invest., 90, pp. 1944-1951
  • Barnes, P.J., Anti-inflammatory actions of glucocorticoids: Molecular mechanisms (1998) Clin. Sci. (Lond.), 94, pp. 557-572
  • Bateman, A., Singh, A., Kral, T., Solomon, S., The immune-hypothalamic-pituitary-adrenal axis (1989) Endocr. Rev., 10, pp. 92-112
  • Belkowsky, S.M., Eisenstein, T.K., Adler, M.W., Rogers, T.J., Inhibition of interleukin-1 and tumor necrosis factor-alpha synthesis following treatment of macrophages with the kappa opioid agonist U50, 488H (1995) J. Pharmacol. Exp. Ther., 273, pp. 1491-1496
  • Besedovsky, H.O., Del Rey, A., Immune-neuro-endocrine interactions: Facts and hypothesis (1996) Endocr. Rev., 17, pp. 64-102
  • Bessler, H., Sztein, M.B., Serrate, S.A., β-Endorphin modulation of IL-1 induced IL-2 production (1990) Immunopharmacology, 19, pp. 5-14
  • Blalock, J.E., A molecular basis for bidirectional communication between the immune and neuroendocrine systems (1989) Physiol. Rev., 69, pp. 1-32
  • Blalock, J.E., β-Endorphin in immune cells (1998) Immunol. Today, 19, pp. 191-192
  • Böyun, W., Separation of lymphocytes from peripheral blood and bone marrow (1968) Scand. J. Clin. Invest., 21 (SUPPL.), pp. 77-89
  • Brown, S.L., Van Epps, D.E., Opioid peptides modulate production of interferon gamma by human mononuclear cells (1986) Cell. Immunol., 103, pp. 19-26
  • Buzzetti, R., McLoughlin, L., Lavender, P.M., Clark, A.J., Rees, L.H., Expression of pro-opiomelanocortin gene and quantification of adrenocorticotropic hormone-like immunoreactivity in human normal peripheral mononuclear cells and lymphoid and myeloid malignancies (1989) J. Clin. Invest., 83, pp. 733-737
  • Cabot, P.J., Carter, L., Gaiddon, C., Zhang, Q., Schafer, M., Loeffler, J.P., Stein, C., Immune cell-derived beta-endorphin. Production, release, and control of inflammatory pain in rats (1997) J. Clin. Invest., 100, pp. 142-148
  • Carr, D.J., DeCosta, B.R., Kim, C.H., Jacobson, A.E., Guarcello, V., Rice, K.C., Blalock, J.E., Opioid receptors on cells of the immune system: Evidence for delta- and kappa-classes (1989) J. Endocrinol., 122, pp. 161-168
  • Carr, D.J., Radulescu, R.T., DeCosta, B.R., Rice, K.C., Blalock, J.E., Differential effect of opioids on immunoglobulin production by lymphocytes isolated from Peyer's patches and spleen (1990) Life Sci., 47, pp. 1059-1069
  • Chao, C.C., Molitor, T.W., Close, K., Hu, S., Peterson, P.K., Morphine inhibits the release of tumor necrosis factor in human peripheral blood mononuclear cell cultures (1993) Int. J. Immunopharmacol., 15, pp. 447-453
  • Chuang, L.F., Chuang, T.K., Killam K.F., Jr., Chuang, A.J., Kung, H.F., Yu, L., Chuang, R.Y., Delta opioid receptor gene expression in lymphocytes (1994) Biochem. Biophys. Res. Commun., 202, pp. 1291-1299
  • Chuang, T.K., Killam K.F., Jr., Chuang, L.F., Kung, H.F., Sheng, W.S., Chao, C.C., Yu, L., Chuang, R.Y., Mu opioid receptor gene expression in immune cells (1995) Biochem. Biophys. Res. Commun., 216, pp. 922-930
  • Fontana, L., Fattorossi, A., D'amelio, R., Migliorati, A., Perricone, R., Modulation of human concanavalin A-induced lymphocyte proliferative response by physiological concentrations of β-endorphin (1987) Immunopharmacology, 13, pp. 111-115
  • Garcia, I., Perez-Castillo, A., Moreno, J., Alemany, S., Beta-endorphin inhibits interleukin-2 release and expression of interleukin-2 receptors in concanavalin A-stimulated splenic lymphocytes (1992) Lymphokine Cytokine Res., 11, pp. 339-345
  • Gilman, S.C., Schwartz, J.M., Milner, R.J., Bloom, F.E., Feldman, J.D., Beta-endorphin enhances lymphocyte proliferative responses (1982) Proc. Natl. Acad. Sci. U. S. A., 79, pp. 4226-4230
  • Gilmore, W., Weiner, L.P., The opioid specificity of beta-endorphin enhancement of murine lymphocyte proliferation (1989) Immunopharmacology, 17, pp. 19-30
  • Giron, I.M., Martinelli, V., Brambilla, E., Furlan, R., Panerai, A.E., Comi, G., Sacerdote, P., Beta-endorphin concentrations in peripheral blood mononuclear cells of patients with multiple sclerosis: Effects of treatment with interferon beta (2000) Arch. Neurol., 57, pp. 1178-1181
  • Gomez-Flores, R., Rice, K.C., Zhang, X., Weber, R.J., Increased tumor necrosis factor-alpha and nitric oxide production by rat macrophages following in vitro stimulation and intravenous administration of the delta-opioid agonist SNC 80 (2001) Life Sci., 68, pp. 2675-2684
  • Guillemin, R., Vargo, T., Rossier, J., Minick, S., Ling, N., Rivier, C., Vale, W., Bloom, F., Beta-endorphin and adrenocorticotropin are selected concomitantly by the pituitary gland (1977) Science, 197, pp. 1367-1369
  • Halford, W.P., Gebhardt, B.M., Carr, D.J., Functional role and sequence analysis of a lymphocyte orphan opioid receptor (1995) J. Neuroimmunol., 59, pp. 91-101
  • Heijnen, C.J., Zijlstra, J., Kavelaars, A., Croiset, G., Ballieux, R.E., Modulation of the immune response by POMC-derived peptides: I. Influence on proliferation of human lymphocytes (1987) Brain Behav. Immun., 1, pp. 284-291
  • Hellbach, S., Gartner, P., Deicke, J., Fischer, D., Hassan, A.H., Almeida, O.F.X., Inherent glucocorticoid response potential of isolated hypothalamic neuroendocrine neurons (1998) FASEB J., 12, pp. 199-207
  • Hosoi, J., Ozawa, H., Granstein, R.D., Beta-endorphin binding and regulation of cytokine expression in Langerhans cells (1999) Ann. N.Y. Acad. Sci., 885, pp. 405-413
  • House, R.V., Thomas, P.T., Bhargava, H.N., A comparative study of immunomodulation produced by in vitro exposure to delta opioid receptor agonist peptides (1996) Peptides, 17, pp. 75-81
  • Jessop, D.S., Central non-glucocorticoid inhibitors of the hypothalamo-pituitary-adrenal axis (1999) J. Endocrinol., 160, pp. 169-180
  • Johnson, H.M., Smith, E.M., Torres, B.A., Blalock, J.E., Regulation of the in vitro antibody response by neuroendocrine hormones (1982) Proc. Natl. Acad. Sci. U. S. A., 79, pp. 4171-4174
  • Jonhson, E.W., Blalock, J.E., Smith, E.M., ACTH receptor-mediated induction of leukocyte cyclic AMP (1988) Biochem. Biophys. Res. Commun., 157, pp. 1205-1211
  • Karanth, S., Linthorst, A.C., Stalla, G.K., Barden, N., Holsboer, F., Reul, J.M.H.M., Hypothalamic-pituitary-adrenocortical axis changes in a transgenic mouse with impaired glucocorticoid receptor function (1997) Endocrinology, 138, pp. 3476-3485
  • Kavelaars, A., Ballieux, R.E., Heijnen, C.J., The role of IL-1 in the corticotropin-releasing factor and arginine-vasopressin-induced secretion of immunoreactive beta-endorphin by human peripheral blood mononuclear cells (1989) J. Immunol., 142, pp. 2338-2342
  • Kavelaars, A., Ballieux, R.E., Heijnen, C.J., In vitro beta-adrenergic stimulation of lymphocyte induces the release of immunoreactive beta-endorphin (1990) Endocrinology, 126, pp. 3028-3032
  • Kavelaars, A., Ballieux, R.E., Heijnen, C.J., Beta-endorphin secretion by human peripheral blood mononuclear cells: Regulation by glucocorticoids (1990) Life Sci., 46, pp. 1233-1240
  • Kavelaars, A., Ballieux, R.E., Heijnen, C.J., Two different signalling pathways for the induction of immunoreactive beta-endorphin secretion by human peripheral blood mononuclear cells (1991) Endocrinology, 128, pp. 765-770
  • Kovalovsky, D., Pereda, M.P., Stalla, G.K., Holsboer, F., Arzt, E., Differential regulation of interleukin-1 receptor antagonist by proopiomelanocortin peptides adrenocorticotropic hormone and beta-endorphin (1999) Neuroimmunomodulation, 6, pp. 367-372
  • Kusnecov, A.W., Husband, A.J., King, M.G., Pang, G., Smith, R., In vivo effects of beta-endorphin on lymphocyte proliferation and interleukin 2 production (1987) Brain Behav. Immun., 1, pp. 88-97
  • Lolait, S.J., Clements, J.A., Markwick, A.J., Cheg, C., McNally, M., Smith, A.I., Fuder, J.W., Pro-opiomelanocortin messenger ribonucleic acid and posttranslational processing of beta endorphin in spleen macrophages (1986) J. Clin. Invest., 77, pp. 1776-1779
  • Lyons, P.D., Blalock, J.E., Pro-opiomelanocortin gene expression and protein processing in rat mononuclear leukocytes (1997) J. Neuroimmunol., 78, pp. 47-56
  • Manfredi, B., Sacerdote, P., Bianchi, M., Locatelli, L., Veljic-Radulovic, J., Panerai, A.E., Evidence for an opioid inhibitory effect on T cell proliferation (1993) J. Neuroimmunol., 44, pp. 43-48
  • Manfredi, B., Clementi, E., Sacerdote, P., Bassetti, M., Panerai, A.E., Age-related changes in mitogen-induced beta-endorphin release from human peripheral blood mononuclear cells (1995) Peptides, 16, pp. 699-706
  • Marx, C., Erhart-Bornstein, M., Scherbaum, W.A., Bornstein, S.R., Regulation of adrenocortical function by cytokines relevance for immune-endocrine interaction (1998) Horm. Metab. Res., 30, pp. 416-420
  • Mathews, P.M., Froelich, C.J., Sibbitt W.L., Jr., Bankhurst, A.D., Enhancement of natural cytotoxicity by beta-endorphin (1983) J. Immunol., 130, pp. 1658-1662
  • McCain, H.W., Lamster, I.B., Bozzone, J.M., Grbic, J.T., Beta-endorphin modulates human immune activity via non-opiate receptor mechanisms (1982) Life Sci., 31, pp. 1619-1624
  • Morch, H.K., Pedersen, B.K., β-Endorphin and the immune system - Possible role in autoimmune diseases (1995) Autoimmunity, 21, pp. 161-171
  • Morgan, E.L., McClurg, M.R., Janda, J.A., Suppression of human B lymphocyte activation by beta-endorphin (1990) J. Neuroimmunol., 28, pp. 209-217
  • Paez Pereda, M., Missale, C., Grubler, Y., Arzt, E., Schaaf, L., Stalla, G.K., Nerve growth factor and retinoic acid inhibit proliferation and invasion in thyroid tumor cells (2000) Mol. Cell. Endocrinol., 167, pp. 99-106
  • Panerai, A.E., Manfredi, B., Granucci, F., Sacerdote, P., The β-endorphin inhibition of mitogen-induced splenocytes proliferation is mediated by central and peripheral paracrine/autocrine effects of the opioid (1995) J. Neuroimmunol., 58, pp. 71-76
  • Panerai, A.E., Sacerdote, P., β-Endorphin in the immune system: A role at last? (1997) Immunol. Today, 18, pp. 317-319
  • Peng, X., Mosser, D.M., Adler, M.W., Rogers, T.J., Meissler J.J., Jr., Eisenstein, T.K., Morphine enhances interleukin-12 and the production of other pro-inflammatory cytokines in mouse peritoneal macrophages (2000) J. Leukoc. Biol., 68, pp. 723-728
  • Przewlocki, R., Hassan, A.H., Lason, W., Epplen, C., Herz, A., Stein, C., Gene expression and localization of opioid peptides in immune cells of inflamed tissue: Functional role in antinociception (1992) Neuroscience, 48, pp. 491-500
  • Puppo, F., Corsini, G., Mangini, P., Bottaro, L., Barreca, T., Influence of beta-endorphin on phytohemagglutinin-induced lymphocyte proliferation and on the expression of mononuclear cell surface antigens in vitro (1985) Immunopharmacology, 10, pp. 119-125
  • Radulescu, R.T., De Costa, B.R., Jacobson, A.E., Rice, K.C., Blalock, J.E., Carr, D.J.J., Biochemical and functional characterization of a μ-opioid receptor binding site on cells of the immune system (1991) Prog. Neuroimmunol., 4, pp. 166-179
  • Raiden, S., Polack, E., Nahmod, V., Labeur, M., Holsboer, F., Arzt, E., TRH receptor on immune cells: In vitro and in vivo stimulation of human lymphocyte and rat splenocyte DNA synthesis by TRH (1995) J. Clin. Immunol., 15, pp. 242-249
  • Reul, J.M., Stec, I., Wiegers, G.J., Labeur, M.S., Linthorst, A.C., Arzt, E., Holsboer, F., Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats (1994) J. Clin. Invest., 93, pp. 2600-2607
  • Roda, L.G., Bongiorno, L., Trani, E., Urbani, A., Marini, M., Positive and negative immunomodulation by opioid peptides (1996) Int. J. Immunopharmacol., 18, pp. 1-16
  • Roy, S., Barke, R.A., Loh, H.H., Mu-opioid receptor-knockout mice: Role of mu-opioid receptor in morphine mediated immune functions (1998) Brain Res., Mol. Brain Res., 61, pp. 190-194
  • Rubinstein, M., Japón, M.A., Low, M.J., Introduction of a point mutation into the mouse genome by homologous recombination in embryonic stem cells using a replacement type vector with a selectable marker (1993) Nucleic Acids Res., 21, pp. 2613-2617
  • Rubinstein, M., Mogil, J.S., Japon, M., Chan, E.C., Allen, R.G., Low, M.J., Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis (1996) Proc. Natl. Acad. Sci. U. S. A., 93, pp. 3995-4000
  • Sacerdote, P., Manfredi, B., Bianchi, M., Panerai, A.E., Intermittent but not continuous inescapable footshock stress affects immune responses and immunocyte beta-endorphin concentrations in the rat (1994) Brain Behav. Immun., 8, pp. 251-260
  • Sacerdote, P., Manfredi, B., Gaspani, L., Panerai, A.E., The opioid antagonist naloxone induces a shift from type 2 to type 1 cytokine pattern in BALB/cJ mice (2000) Blood, 95, pp. 2031-2036
  • Sapolsky, R.M., Romero, L.M., Munck, A.U., How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions (2000) Endocr. Rev., 21, pp. 55-89
  • Shahabi, N.A., Sharp, B.M., Antiproliferative effects of delta opioids on highly purified CD4+ and CD8+ murine T cells (1995) J. Pharmacol. Exp. Ther., 273, pp. 1105-1113
  • Sharp, B.M., Li, M.D., Matta, S.G., McAllen, K., Shahabi, N.A., Expression of delta opioid receptors and transcripts by splenic T cells (2000) Ann. N.Y. Acad. Sci., 917, pp. 764-770
  • Smith, E.M., Blalock, J.E., Human lymphocyte production of corticotropin and endorphin-like substances: Association with leukocyte interferon (1981) Proc. Natl. Acad. Sci. U. S. A., 78, pp. 7530-7534
  • Smith, E.M., Morrill, A.C., Meyer W.J. III, Blalock, J.E., Corticotropin releasing factor induction of leukocyte-derived immunoreactive ACTH and endorphins (1986) Nature, 321, pp. 881-882
  • Solerte, S.B., Fioravanti, M., Petraglia, F., Facchinetti, F., Patti, A.L., Schifino, N., Genazzani, A.R., Ferrari, E., Plasma beta-endorphin, free fatty acids and blood lipid changes in type 2 (non-insulin dependent) diabetic patients (1988) J. Endocrinol. Investig., 11, pp. 37-42
  • Taub, D.D., Eisenstein, T.K., Geller, E.B., Adler, M.W., Rogers, T.J., Immunomodulatory activity of mu- and kappa-selective opioid agonists (1991) Proc. Natl. Acad. Sci. U. S. A., 88, pp. 360-364
  • Van den Bergh, P., Rozing, J., Nagelkerken, L., Opioid peptides as cytokines in T cell activation (1991) Adv. Neuroimmunol., 1, pp. 189-203
  • Van den Bergh, P., Rozing, J., Nagelkerken, L., Two opposing modes of action of beta-endorphin on lymphocyte function (1991) Immunology, 72, pp. 537-543
  • Van Epps, D.E., Saland, L., Beta-endorphin and met-enkephalin stimulate human peripheral blood mononuclear cell chemotaxis (1984) J. Immunol., 132, pp. 3046-3053
  • Whitnall, M.H., Regulation of the hypothalamic corticotropin-releasing hormone neurosecretory system (1993) Prog. Neurobiol., 40, pp. 573-629
  • Wiedermann, C.J., Sacerdote, P., Mur, E., Kinigadner, U., Wicker, T., Panerai, A.E., Braunsteiner, H., Decreased immunoreactive beta-endorphin in mononuclear leucocytes from patients with rheumatic diseases (1992) Clin. Exp. Immunol., 87, pp. 178-182
  • Wiedermann, C.J., Sacerdote, P., Propst, A., Propst, T., Judmaier, G., Kathrein, H., Vogel, W., Panerai, A.E., Decreased beta-endorphin content in peripheral blood mononuclear leukocytes from patients with Crohn's disease (1994) Brain Behav. Immun., 8, pp. 261-269
  • Wiegers, G.J., Labeur, M.S., Stec, I.E., Klinkert, W.E., Holsboer, F., Reul, J.M., Glucocorticoids accelerate anti-T cell receptor-induced T cell growth (1995) J. Immunol., 155, pp. 1893-1902
  • Wiegers, G.J., Stec, I.E., Klinkert, W.E., Reul, J.M., Glucocorticoids regulate TCR-induced elevation of CD4: Functional implications (2000) J. Immunol., 164, pp. 6213-6220

Citas:

---------- APA ----------
Refojo, D., Kovalovsky, D., Young, J.I., Rubinstein, M., Holsboer, F., Reul, J.M.H.M, Low, M.J.,..., Arzt, E. (2002) . Increased splenocyte proliferative response and cytokine production in β-endorphin-deficient mice. Journal of Neuroimmunology, 131(1-2), 126-134.
http://dx.doi.org/10.1016/S0165-5728(02)00268-0
---------- CHICAGO ----------
Refojo, D., Kovalovsky, D., Young, J.I., Rubinstein, M., Holsboer, F., Reul, J.M.H.M, et al. "Increased splenocyte proliferative response and cytokine production in β-endorphin-deficient mice" . Journal of Neuroimmunology 131, no. 1-2 (2002) : 126-134.
http://dx.doi.org/10.1016/S0165-5728(02)00268-0
---------- MLA ----------
Refojo, D., Kovalovsky, D., Young, J.I., Rubinstein, M., Holsboer, F., Reul, J.M.H.M, et al. "Increased splenocyte proliferative response and cytokine production in β-endorphin-deficient mice" . Journal of Neuroimmunology, vol. 131, no. 1-2, 2002, pp. 126-134.
http://dx.doi.org/10.1016/S0165-5728(02)00268-0
---------- VANCOUVER ----------
Refojo, D., Kovalovsky, D., Young, J.I., Rubinstein, M., Holsboer, F., Reul, J.M.H.M, et al. Increased splenocyte proliferative response and cytokine production in β-endorphin-deficient mice. J. Neuroimmunol. 2002;131(1-2):126-134.
http://dx.doi.org/10.1016/S0165-5728(02)00268-0