Neuroimmunomodulation: effects of drugs, stress and cytocines on central nervous and immune systems bidirectional relationships

• Grant number: 04/14128-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: May 01, 2005
• End date: May 31, 2009
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: João Palermo Neto
• Grantee: João Palermo Neto
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Frederico Azevedo da Costa Pinto ; Luiz Carlos de Sá-Rocha
• Associated scholarship(s): 09/01826-4 - Glutamatergic and enkephalinergic participation in effects induced by amphetamine on the mice's pulmonary allergic inflammatory response, BP.MS; 06/54587-9 - Effects of prenatal administration of LPS on the dopaminergic and serotonergic central systems of male rat offspring, BP.MS

Abstract

The matter of possible relationships between emotions and the occurrence of disease has intrigued scientific and academic communities, as well as the popular culture worldwide. Science has never had such an enormous collection of apparatuses, techniques and, on top of all, knowledge that may be applied to the expansion of this field as it does nowadays. The ever increasing body of knowledge in immunology and neurology has allowed the discovery of receptors for a series of neurotransmitters on cells of the immune system (IS) as well as on both central and peripheral lymphoid organs. Evidences have accumulated (in vitro and in vivo) supporting the notion that stress, anxiety and chemical substances with known central effects (benzodiazepines and haloperidol) may, as a matter of fact, interfere with the activity of the IS, probably by means of hypothalamus-pituitary-adrenal (HP A) axis activation, along with modulation of the sympathetic branch of the autonomic nervous system (SNS). On the other hand, it is widely described that immune responses may alter the activity of the central nervous system (CNS), and that several behavioral changes are driven by circulating cytokines, for example, the interleukins (ILs) 1 and 6. We have employed in our labs a rational approach to the interactions between stress and anxiety, and increased susceptibility to disease. We have also focused on the effects over the immune system of molecules with known effects on the CNS. Additionally, we have studied the behavioral changes that are associated with immune reactions (such as allergies) and infectious diseases. This project aims on following up the ongoing research developed in our labs. We particularly intend to evaluate, by means of nineteen individual projects (undergraduate students enrolled on introduction to research, graduate students with ongoing masters or PhD projects, and post-doctoral fellows with individual projects) the following aspects of this field: (1) the effects of stress (prenatal or during adulthood) on parameters of inflammatory and immune responses; (2) the effects of chemical substances (benzodiazepines, haloperidol, imipramine, picrotoxin, cyhalothrin, MDMA ("ecstasy") and the extract of Chlorela vulgaris) on parameters of inflammatory and immune responses; (3) the neurobehavioral and neurochemical effects of the administration of LPS, IL-1ß or TNF-a; (4) behavioral and neurochemical changes induced immunologically through different models; (5) the effects of LPS administration on dominance relationship in mice; (6) the effects of substance P and of anti-inflammatory molecules on LPS-induced sickness behavior; and (7) the influence of female sex hormones on inflammatory and immune reactions. (AU)

Scientific publications

(43)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALVES, GLAUCIE J.; RIBEIRO, ALISON; PALERMO-NETO, JOAO. The neuroimmune changes induced by cohabitation with an Ehrlich tumor-bearing cage mate rely on olfactory information. BRAIN BEHAVIOR AND IMMUNITY, v. 26, n. 1, p. 32-39, JAN 2012. (04/14128-0, 99/04228-7)

TOMIYOSHI, M. Y.; SAKAI, M.; BALEEIRO, R. B.; STANKEVICIUS, D.; MASSOCO, C. O.; PALERMO-NETO, J.; BARBUTO, J. A. M.. Cohabitation with a B16F10 melanoma-bearer cage mate influences behavior and dendritic cell phenotype in mice. BRAIN BEHAVIOR AND IMMUNITY, v. 23, n. 4, p. 558-567, MAY 2009. (04/14128-0, 04/09956-0)

FERRAZ-DE-PAULA, V.; STANKEVICIUS, D.; RIBEIRO, A.; PINHEIRO, M. L.; RODRIGUES-COSTA, E. C.; FLORIO, J. C.; LAPACHINSKE, S. F.; MOREAU, R. L. M.; PALERMO-NETO, J.. Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice. Brazilian Journal of Medical and Biological Research, v. 44, n. 5, p. 428-437, MAY 2011. (04/14128-0)

ROTH CARVALHO-FREITAS, MARIA ISABEL; ANSELMO-FRANCI, JANETE A.; MAIORKA, PAULO CESAR; PALERMO-NETO, JOAO; FELICIO, LUCIANO F.. Prolactin differentially modulates the macrophage activity of lactating rats: possible role of reproductive experience. JOURNAL OF REPRODUCTIVE IMMUNOLOGY, v. 89, n. 1, p. 38-45, APR 2011. (04/14128-0)

DE PAULA, VIVIANE FERRAZ; RIBEIRO, ALISON; PINHEIRO, MILENA L.; SAKAI, MONICA; LACAVA, MARIANA C. R.; LAPACHINSKE, SILVIO F.; MOREAU, REGINA L. M.; PALERMO-NETO, JOAO. Methylenedioxymethamphetamine (Ecstasy) Decreases Neutrophil Activity and Alters Leukocyte Distribution in Bone Marrow, Spleen and Blood. NEUROIMMUNOMODULATION, v. 16, n. 3, p. 191-200, 2009. (04/14128-0)

VICTONI, TATIANA; COELHO, FERNANDO RODRIGUES; SOARES, ALEXANDRE LEARTH; DE FREITAS, ANDRESSA; SECHER, THOMAS; GUABIRABA, RODRIGO; ERARD, FRANCOIS; DE OLIVEIRA-FILHO, RICARDO MARTINS; VARGAFTIG, B. BORIS; LAUVAUX, GREGOIRE; et al. Local and remote tissue injury upon intestinal ischemia and reperfusion depends on the TLR/MyD88 signaling pathway. MEDICAL MICROBIOLOGY AND IMMUNOLOGY, v. 199, n. 1, p. 35-42, FEB 2010. (04/14128-0)

SOARES, ALEXANDRE LEARTH; COELHO, FERNANDO RODRIGUES; GUABIRABA, RODRIGO; KAMAL, MAMDOUH; BORIS VARGAFTIG, B.; LI, LILY; LI, JIAN; TAVARES-DE-LIMA, WOTHAN; RYFFEL, BERNHARD. TUMOR NECROSIS FACTOR IS NOT ASSOCIATED WITH INTESTINAL ISCHEMIA/REPERFUSION-INDUCED LUNG INFLAMMATION. Shock, v. 34, n. 3, p. 306-313, SEP 2010. (04/14128-0)

LAZZARINI, R.; SAKAI, M.; COSTA-PINTO, F. A.; PALERMO-NETO, J.. Diazepam decreases leukocyte-endothelium interactions in situ. Immunopharmacology and Immunotoxicology, v. 32, n. 3, p. 402-409, SEP 2010. (04/14128-0)

QUINTEIRO-FILHO, W. M.; RIGHI, D. A.; PALERMO-NETO, J.. Effect of cyhalothrin on Ehrlich tumor growth and macrophage activity in mice. Brazilian Journal of Medical and Biological Research, v. 42, n. 10, p. 912-917, OCT 2009. (04/14128-0)

RIBEIRO, ALISON; FERRAZ-DE-PAULA, VIVIANE; PINHEIRO, MILENA L.; SAKAI, MONICA; COSTA-PINTO, FREDERICO A.; PALERMO-NETO, JOAO. Anandamide prior to sensitization increases cell-mediated immunity in mice. International Immunopharmacology, v. 10, n. 4, p. 431-439, APR 2010. (04/14128-0)

KIRSTEN, THIAGO B.; TARICANO, MARINA; MAIORKA, PAULO C.; PALERMO-NETO, JOAO; BERNARDI, MARIA M.. Prenatal Lipopolysaccharide Reduces Social Behavior in Male Offspring. NEUROIMMUNOMODULATION, v. 17, n. 4, p. 240-251, 2010. (06/54587-9, 04/14128-0)

CARVALHO-FREITAS‚ MIR; ANSELMO-FRANCI‚ JA; TEODOROV‚ E.; NASELLO‚ AG; PALERMO-NETO‚ J.; FELICIO‚ LF. Reproductive experience modifies dopaminergic function‚ serum levels of prolactin‚ and macrophage activity in female rats. Life Sciences, v. 81, n. 2, p. 128-136, 2007. (04/14128-0)

COELHO‚ F.R.; CAVRIANI‚ G.; SOARES‚ A.L.; TEIXEIRA‚ S.A.; ALMEIDA‚ P.C.L.; SUDO-HAYASHI‚ L.S.; MUSCARÁ‚ M.N.; OLIVEIRA-FILHO‚ R.M.; VARGAFTIG‚ B.B.; TAVARES-DE-LIMA‚ W.. LYMPHATIC-BORNE IL-1 [beta] AND THE INDUCIBLE ISOFORM OF NITRIC OXIDE SYNTHASE TRIGGER THE BRONCHIAL HYPORESPONSIVENESS AFTER INTESTINAL ISCHEMA/REPERFUSION IN RATS. Shock, v. 28, n. 6, p. 694-699, 2007. (04/14128-0)

LIGEIRO DE OLIVEIRA, ANA PAULA; SCHATZMANN PERON, JEAN PIERRE; DAMAZO, AMILCAR SABINO; DOS SANTOS FRANCO, ADRIANA LINO; DOMINGOS, HELORI VANNI; OLIANI, SONIA MARIA; OLIVEIRA-FILHO, RICARDO MARTINS; VARGAFTIG, BERNARDO BORIS; TAVARES-DE-LIMA, WOTHAN. Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats. RESPIRATORY RESEARCH, v. 11, p. 115, 2010. (09/07208-0, 04/14128-0)

FONSECA‚ E.S.M.; SAKAI‚ M.; CARVALHO-FREITAS‚ M.I.R.; PALERMO NETO‚ J.. Naloxone treatment prevents prenatal stress effects on peritoneal macrophage activity in mice offspring. Neuroendocrinology, v. 81, n. 5, p. 322-328, 2005. (04/14128-0)

ALVES‚ G.J.; VISMARI‚ L.; PALERMO-NETO‚ J.. Cohabitation with a sick cage mate: effects on ascitic form of Ehrlich tumor growth and macrophage activity. NEUROIMMUNOMODULATION, v. 14, n. 6, p. 297-303, 2007. (04/14128-0, 99/04228-7)

SAKAI‚ M.; FONSECA‚ ESM; DAGLI‚ MLZ; PALERMO-NETO‚ J.. Diazepam effects on Ehrlich tumor growth and macrophage activity in mice. Life Sciences, v. 78, n. 16, p. 1777-1783, 2006. (04/14128-0)

LIGEIRO DE OLIVEIRA‚ AP; LAZZARINI‚ R.; CAVRIANI‚ G.; QUINTEIRO-FILHO‚ WM; TAVARES DE LIMA‚ W.; PALERMO-NETO‚ J.. Effects of single or repeated amphetamine treatment and withdrawal on lung allergic inflammation in rats. International Immunopharmacology, v. 8, n. 9, p. 1164-1171, 2008. (04/14128-0)

PINHEIRO, MILENA LOBAO; FERRAZ-DE-PAULA, VIVIANE; RIBEIRO, ALISON; SAKAI, MONICA; BERNARDI, MARIA MARTHA; PALERMO-NETO, JOAO. Long-Term Maternal Separation Differentially Alters Serum Corticosterone Levels and Blood Neutrophil Activity in A/J and C57BL/6 Mouse Offspring. NEUROIMMUNOMODULATION, v. 18, n. 3, p. 184-190, 2011. (04/14128-0)

FUKUMASU, HEIDGE; LATORRE, ANDREIA OLIVEIRA; ZAIDAN-DAGLI, MARIA LUCIA. Paullinia cupana Mart. var. sorbilis, Guarana, Increases Survival of Ehrlich Ascites Carcinoma (EAC) Bearing Mice by Decreasing Cyclin-D1 Expression and Inducing a G0/G1 Cell Cycle Arrest in EAC Cells. Phytotherapy Research, v. 25, n. 1, p. 11-16, JAN 2011. (04/14128-0)

LIGEIRO DE OLIVEIRA, ANA PAULA; SCHATZMANN PERON, JEAN PIERRE; DAMAZO, AMILCAR SABINO; DOS SANTOS FRANCO, ADRIANA LINO; DOMINGOS, HELORI VANNI; OLIANI, SONIA MARIA; OLIVEIRA-FILHO, RICARDO MARTINS; VARGAFTIG, BERNARDO BORIS; TAVARES-DE-LIMA, WOTHAN. Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats. RESPIRATORY RESEARCH, v. 11, p. 12-pg., 2010-08-24. (09/07208-0, 04/14128-0, 09/51886-3)

MATSUZAKI‚ P.; HARAGUCHI‚ M.; AKISUE‚ G.; OLORIS‚ S.C.S.; NAGAMINE‚ M.K.; DA SILVA‚ T.C.; SAKAI‚ M.; FONSECA‚ E.S.M.; PALERMO-NETO‚ J.; LIMA GÓRNIAK‚ S.; et al. Antineoplastic effects of butanolic residue of Pfaffia paniculata. Cancer Letters, v. 238, n. 1, p. 85-89, 2006. (04/14128-0)

COSTA-PINTO‚ F.A.; BASSO‚ A.S.; DE SÁ-ROCHA‚ L.C.; BRITTO‚ L.R.G.; RUSSO‚ M.; PALERMO-NETO‚ J.. Neural Correlates of IgE-Mediated Allergy. Annals of the New York Academy of Sciences, v. 1088, n. 1, p. 116-131, 2006. (04/14128-0, 99/04228-7, 99/03778-3, 01/13510-0)

ALVES‚ G.J.; VISMARI‚ L.; FLORIO‚ J.C.; PALERMO-NETO‚ J.. Cohabitation with a sick cage mate: effects on noradrenaline turnover and neutrophil activity. NEUROSCIENCE RESEARCH, v. 56, n. 2, p. 172-179, 2006. (04/14128-0, 99/04228-7)

SA-ROCHA‚ VM; SA-ROCHA‚ LC; PALERMO-NETO‚ J.. Variations in behavior‚ innate immunity and host resistance to B16F10 melanoma growth in mice that present social stable hierarchical ranks. Physiology & Behavior, v. 88, n. 1, p. 108-115, 2006. (04/14128-0)

GLAUCIE JUSSILANE ALVES; JOÃO PALERMO-NETO. Neuroimunomodulação: sobre o diálogo entre os sistemas nervoso e imune. Revista Brasileira de Psiquiatria, v. 29, n. 4, p. 363-369, 2007-08-03. (99/04228-7, 04/14128-0)

KIRSTEN, THIAGO BERTI; TARICANO, MARINA; FLORIO, JORGE CAMILO; PALERMO-NETO, JOAO; BERNARDI, MARIA MARTHA. Prenatal lipopolysaccharide reduces motor activity after an immune challenge in adult male offspring. Behavioural Brain Research, v. 211, n. 1, p. 77-82, JUL 29 2010. (06/54587-9, 04/14128-0)

BERNARDI, MARIA M.; KIRSTEN, THIAGO B.; MATSUOKA, SUZANA M.; TEODOROV, ELIZABETH; HABR, SORAYA F.; PENTEADO, SANDRA H. W. N.; PALERMO-NETO, JOAO. Prenatal Lipopolysaccharide Exposure Affects Maternal Behavior and Male Offspring Sexual Behavior in Adulthood. NEUROIMMUNOMODULATION, v. 17, n. 1, p. 47-55, 2010. (04/14128-0)

ZARZANA, EDUARDO C.; BASSO, ALEXANDRE S.; COSTA-PINTO, FREDERICO A.; PALERMO-NETO, JOAO. Pharmacological Manipulation of Immune-Induced Food Aversion in Rats. NEUROIMMUNOMODULATION, v. 16, n. 1, p. 19-27, 2009. (04/14128-0)

KIRSTEN, THIAGO BERTI; SOARES DE OLIVEIRA, BEATRIZ PETRI; LIGEIRO DE OLIVEIRA, ANA PAULA; KIELING, KARIN; DE LIMA, WOTHAN TAVARES; PALERMO-NETO, JOAO; BERNARDI, MARIA MARTHA. Single early prenatal lipopolysaccharide exposure prevents subsequent airway inflammation response in an experimental model of asthma. Life Sciences, v. 89, n. 1-2, p. 15-19, JUL 4 2011. (04/14128-0)

RIBEIRO, A.; FERRAZ-DE-PAULA, V.; PINHEIRO, M. L.; PALERMO-NETO, J.. Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests. Brazilian Journal of Medical and Biological Research, v. 42, n. 6, p. 556-560, JUN 2009. (04/14128-0)

DE LIMA, CAMILA BENTO; SAKAI, MONICA; LATORRE, ANDREIA OLIVEIRA; DE MORAES MOREAU, REGINA LUCIA; PALERMO-NETO, JODO. Effects of different closes and schedules of diazepam treatment on lymphocyte parameters in rats. International Immunopharmacology, v. 10, n. 11, p. 1335-1343, NOV 2010. (04/14128-0)

CARVALHO-FREITAS, MARIA I. R.; RODRIGUES-COSTA, ELAINE C.; NASELLO, ANTONIA G.; PALERMO-NETO, JOAO; FELICIO, LUCIANO F.. In vitro macrophage activity: Biphasic effect of prolactin and indirect evidence of dopaminergic modulation. NEUROIMMUNOMODULATION, v. 15, n. 2, p. 131-139, 2008. (04/14128-0)

SAKAI, M.; FERRAZ-DE-PAULA, V.; PINHEIRO, M. L.; RIBEIRO, A.; QUINTEIRO-FILHO, W. M.; RONE, M. B.; MARTINEZ-ARGUELLES, D. B.; DAGLI, M. L. Z.; PAPADOPOULOS, V.; PALERMO-NETO, J.. Translocator protein (18 kDa) mediates the pro-growth effects of diazepam on Ehrlich tumor cells in vivo. European Journal of Pharmacology, v. 626, n. 2-3, p. 131-138, JAN 25 2010. (04/14128-0)

VISMARI, L.; ALVES, G. J.; PALERMO-NETO, J.. Amitriptyline and Acute Inflammation: A Study Using Intravital Microscopy and the Carrageenan-Induced Paw Edema Model. Pharmacology, v. 86, n. 4, p. 231-239, 2010. (04/14128-0, 99/04228-7)

RIGHI, D. A.; XAVIER, F. G.; PALERMO-NETO, J.. Cyhalothrin increased c-fos immunoreactivity at the paraventricular nucleus of the hypothalamus in rats, and suppressed macrophage activity in an adrenal-dependent fashion. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, v. 27, n. 1, p. 96-102, JAN 2009. (04/14128-0)

KINOSHITA, DENISE; HAMADA COHN, DANIEL WAGNER; COSTA-PINTO, FREDERICO AZEVEDO; DE SA-ROCHA, LUIZ CARLOS. Behavioral effects of LPS in adult, middle-aged and aged mice. Physiology & Behavior, v. 96, n. 2, p. 328-332, FEB 16 2009. (04/14128-0)

COHN, DANIEL W. H.; DE SA-ROCHA, LUIZ C.. Sickness and Aggressive Behavior in Dominant and Subordinate Mice. Ethology, v. 115, n. 2, p. 112-121, FEB 2009. (04/14128-0)

RIGHI, D. A.; XAVIER, F. G.; PALERMO-NETO, J.. Effects of type II pyrethroid cyhalothrin on rat innate immunity: A flow cytometric study. International Immunopharmacology, v. 9, n. 1, p. 148-152, JAN 2009. (04/14128-0)

COSTA-PINTO, FREDERICO AZEVEDO; BASSO, ALEXANDRE SALGADO; RUSSO, MOMTCHILO. Role of mast cell degranulation in the neural correlates of the immediate allergic reaction in a murine model of asthma. BRAIN BEHAVIOR AND IMMUNITY, v. 21, n. 6, p. 783-790, Aug. 2007. (04/14297-6, 04/14128-0)

PALERMO-NETO, J.; FONSECA, E. S. M.; QUINTEIRO-FILHO, W. M.; CORREIA, C. S. C.; SAKAI, M.. Effects of individual housing on behavior and resistance to Ehrlich tumor growth in mice. Physiology & Behavior, v. 95, n. 3, p. 435-440, OCT 20 2008. (04/14128-0)

ALVES, GLAUCIE JUSSILANE; VISMARI, LUCIANA; LAZZARINI, RICARDO; BERNARDINO MERUSSE, JOSE LUIS; PALERMO-NETO, JOAO. Odor cues from tumor-bearing mice induces neuroimmune changes. Behavioural Brain Research, v. 214, n. 2, p. 357-367, DEC 10 2010. (04/14128-0, 99/04228-7)

VISMARI, LUCIANA; ALVES, GLAUCIE J.; MUSCARA, MARCELO N.; PALERMO-NETO, JOAO. A possible role to nitric oxide in the anti-inflammatory effects of amitriptyline. Immunopharmacology and Immunotoxicology, v. 34, n. 4, p. 578-585, AUG 2012. (04/14128-0)