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First international workshop on neuroimmunomodulation (NIM)
Journal of Neuroimmunologr', l0 (1985) 97-99 Elsevier
97
JNI 00334
Conference Report
First International Workshop on Neuroimmunomodulation (NIM) A.P. K e r z a - K w i a t e c k i Health Scientist Administrator, Demyelinating, Atrophic, and Dementing Disorders Program, National Institute of Neurological and Communicatioe Disorders and Stroke, National Institutes of Health, Bethesda, MD 20205 (U.S.A.) (Received 5 July, 1985) (Revised, received 25 July, 1985) (Accepted 25 July, 1985)
The First International Workshop on Neuroimmunomodulation (NIM) was held November 27-30, 1984 at the National Institutes of Health in Bethesda, MD, U.S.A. About 150 scientists from 12 countries, East and West, attended. Sixty major fields of research were represented with the main contributions coming from immunology and neurobiology. Of 90 abstracts submitted, 70 were presented [1]. The general impression of participants in the meeting was that NIM has come a long way from relative obscurity. The Workshop created a fertile ground for discussion of the new ideas in this field as well as providing some surprises in the more 'esoteric' investigations which are being undertaken. Many presentations and interviews resulted in several lay and professionally oriented reports. One such review is quite extensive [2]. The program of presentations, papers and round-table discussions focused on the following 3 major themes: growing evidence in support of nervous-immune interrelationships; the role, localization and function of hormone receptors; and the psychological and behavioral aspects of NIM [3]. Since space will not permit all of the science presented to be covered, the following examples are selected to provide an overall impression. The source and intrathymic distribution of cholinergic and catecholaminergic nerves was demonstrated. Autonomic nerve fibers were found in a consistent topographical relation within the thymus and appear to play a role in thymus maturation [4]. Experimentally decreased concentrations of cerebral norepinephrine were shown to be followed by decrease in the primary IgM and IgG immune response. In addition, norepinephrine infusion into human volunteers increased the activity of natural killer cells [5]. Data were also presented to show that acetylcholine can stimulate IgG synthesis [6]. Polyinosinic : polycytidylic acid (poly IC), which elevates natural killer cell (NK) 0165-5728/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)
98 activity in mice, was paired to a conditioned stimulus (odor of camphor) in 9 association trials. 72 h after the final association trial, one group of mice was exposed to the conditioned stimulus alone and significant enhancement of natural killer cell activity was observed in all animals. Five different control groups were simultaneously monitored. The experiment showed a large increase in a host defense response, in which every animal in the conditioned experimental group responded in the total absence of the original inducer (poly IC). The conditioned group showed a 3-fold increase of N K activity over the negative control and a 39-fold increase over saline-plus-camphor control groups. This was the first demonstration that N K activity could be conditioned using classical Pavlovian techniques [7]. In a related double-blind clinical trial of interferon, the immunological effect of a placebo was observed in induction of N K activity [8]. The role of the anterior hypothalamus in the regulation of an autoimmune disease (EAE) was further confirmed [9]. Antiserum against testis or corpus luteum reacted with the hypothalamus, demonstrating that the central nervous system contains cross-reactive organ-specific antigen(s) [10]. This observation raises questions about possible CNS involvement in other autoimmune disorders. Another presentation indicated that opiates, alcohol and cocaine modulate T-cell receptors and antigenic markers, thus implicating a possible role for mood-altering drugs in the development of immune dysfunction [11]. It is known that lymphocytes have receptors for hormones which can modulate their function. One presentation addressed this relationship in an experiment where non-human infant primates were separated from their mothers. Significant endocrine-mediated immunological changes were observed [12]. Interestingly, meditation was shown to suppress cell-mediated immune responses to varicella zoster virus, as measured by an in vitro delayed hypersensitivity skin test, and a lymphocyte blastogenic response [13]. It was shown that in some patients with malignant melanoma, the patient's emotional status (as well as tumor-host response factors such as mitotic rate and lymphocytic infiltration) could affect the prognosis [141. In conclusion, it appears that some of the newer concepts of NIM might enlarge research horizons and accelerate scientific discoveries. Chronobiology, immunopsychology and many other aspects of NIM appear to have attained a new degree of scientific legitimacy. NIM could well also expand horizons for the development of treatment and prevention strategies. The Second International Workshop on Neuroimmunomodulation (NIM) will be held June 1-6, 1986 in Dubrovnik, Yugoslavia. This meeting will be open. In addition, by invitation only, a satellite workshop titled NIM: Intervention in Aging and Cancer will follow on %11 June, 1986, in Stromboli, Sicily, Italy [15].
References
1. Proceedings of the First International Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, (in press); 'Neuroimmunomodulation',Gordon and Breach Science Publishers,
99
2. 3. 4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
New York (accepted for publication); Information regarding the above contact: N.H. Spector, FNP, NINCDS. NIH, Federal Building, Room 916, Bethesda, MD 20205, U.S.A. Blalock, J.E. and E.M. Smith, The immune system: our mobile brain?, Immunol. Today, 6 (4) (1985) 115-117. Kerza-Kwiatecki, A.P. and P.Y. Paterson, Neuroimmunomodulation Workshop Report, Clin. Immunol. Immunopathol., 1985, in press. Bulloch, K. and M.R. Cullen, A Comparative Study of the Autonomic Nervous System Innervation of the Thymus in the Mouse and Chicken (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Locke, S., L. Kraus, I. Kutz, S. Edbril, K. Phillips and H. Benson, Altered Natural Killer Cell Activity during Norepinephrine Infusion in Humans (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation, (NIM), IWGN, Bethesda, MD, 1985, in press. Kozlov, V.A. and V.V. Abramov, The Influence of Acetylcholine on the lgG Synthesis and Lymphocyte Proliferation In Vitro (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Solvason, H.B., V.K. Ghanta, R.N. Hiramoto and N.H. Spector, Augmentation of Host-Defense Response (Natural Killer Cell Activity) by a Conditioned Stimulus Only (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Hirsch, R. and K.P. Johnson, Placebo Induced Enhancement of Natural Killer Cell Activity in a Double Blind Trial of Recombinant Alpha 2 Interferon in Multiple Sclerosis Patients (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Wertman, E., H. Ovadia and O. Abramsky, Prevention of Experimental Autoimmune Disease by Anterior Hypothalamus Lesions in Rat (Abstract), First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Paterson, P.Y. and S.M. Harwin, In Vivo Cross Reactivity of Central Nervous System (CNS), Testes and Ovary Tissue Causes Two Types of CNS Lesions in Rat Sensitized to these Tissues (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Donahoe, R.M., J.J. Madden, F. Hollingsworth, D.A. Shafer, A. Falek, J.K.A. Nicholson and P. Bokos, Immunomodulation by Behaviorally Active Drugs Provides a Paradigm for Connecting AIDS-Like Processes and Psychoneuroimmunology (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Coe, C.L., L.T. Rosenberg and S. Levine, Immunological Consequences of Maternal Separation in Infant Primates (Abstract), First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Kelley, K.W., R. Dantzer and P. Mormede, The Role of Conditioning in Delayed-Type Hypersensitivity Immune Responses (Abstract), First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Temoshok, L., R.W. Sagebiel and D.M. Sweet, Psychosocial Factors Associated with Tumor-Host Response in Cutaneous Malignant Melanoma (Abstract), First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. For further information on the Dubrovnik meeting, contact Dr. B. Jankovic, Immunology Research Center, Vojvode Stepe 458, 11221 Belgrade, Yugoslavia, Telephone: (11) 467-465; and on the Stromboli meeting Dr. Walter Pierpaoli, Institute Integrative Biomedical Research, Lohwisstrasse 50, CH-8123 Ebmatingen, Switzerland, Telephone: 01-980-22-66.
97
JNI 00334
Conference Report
First International Workshop on Neuroimmunomodulation (NIM) A.P. K e r z a - K w i a t e c k i Health Scientist Administrator, Demyelinating, Atrophic, and Dementing Disorders Program, National Institute of Neurological and Communicatioe Disorders and Stroke, National Institutes of Health, Bethesda, MD 20205 (U.S.A.) (Received 5 July, 1985) (Revised, received 25 July, 1985) (Accepted 25 July, 1985)
The First International Workshop on Neuroimmunomodulation (NIM) was held November 27-30, 1984 at the National Institutes of Health in Bethesda, MD, U.S.A. About 150 scientists from 12 countries, East and West, attended. Sixty major fields of research were represented with the main contributions coming from immunology and neurobiology. Of 90 abstracts submitted, 70 were presented [1]. The general impression of participants in the meeting was that NIM has come a long way from relative obscurity. The Workshop created a fertile ground for discussion of the new ideas in this field as well as providing some surprises in the more 'esoteric' investigations which are being undertaken. Many presentations and interviews resulted in several lay and professionally oriented reports. One such review is quite extensive [2]. The program of presentations, papers and round-table discussions focused on the following 3 major themes: growing evidence in support of nervous-immune interrelationships; the role, localization and function of hormone receptors; and the psychological and behavioral aspects of NIM [3]. Since space will not permit all of the science presented to be covered, the following examples are selected to provide an overall impression. The source and intrathymic distribution of cholinergic and catecholaminergic nerves was demonstrated. Autonomic nerve fibers were found in a consistent topographical relation within the thymus and appear to play a role in thymus maturation [4]. Experimentally decreased concentrations of cerebral norepinephrine were shown to be followed by decrease in the primary IgM and IgG immune response. In addition, norepinephrine infusion into human volunteers increased the activity of natural killer cells [5]. Data were also presented to show that acetylcholine can stimulate IgG synthesis [6]. Polyinosinic : polycytidylic acid (poly IC), which elevates natural killer cell (NK) 0165-5728/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)
98 activity in mice, was paired to a conditioned stimulus (odor of camphor) in 9 association trials. 72 h after the final association trial, one group of mice was exposed to the conditioned stimulus alone and significant enhancement of natural killer cell activity was observed in all animals. Five different control groups were simultaneously monitored. The experiment showed a large increase in a host defense response, in which every animal in the conditioned experimental group responded in the total absence of the original inducer (poly IC). The conditioned group showed a 3-fold increase of N K activity over the negative control and a 39-fold increase over saline-plus-camphor control groups. This was the first demonstration that N K activity could be conditioned using classical Pavlovian techniques [7]. In a related double-blind clinical trial of interferon, the immunological effect of a placebo was observed in induction of N K activity [8]. The role of the anterior hypothalamus in the regulation of an autoimmune disease (EAE) was further confirmed [9]. Antiserum against testis or corpus luteum reacted with the hypothalamus, demonstrating that the central nervous system contains cross-reactive organ-specific antigen(s) [10]. This observation raises questions about possible CNS involvement in other autoimmune disorders. Another presentation indicated that opiates, alcohol and cocaine modulate T-cell receptors and antigenic markers, thus implicating a possible role for mood-altering drugs in the development of immune dysfunction [11]. It is known that lymphocytes have receptors for hormones which can modulate their function. One presentation addressed this relationship in an experiment where non-human infant primates were separated from their mothers. Significant endocrine-mediated immunological changes were observed [12]. Interestingly, meditation was shown to suppress cell-mediated immune responses to varicella zoster virus, as measured by an in vitro delayed hypersensitivity skin test, and a lymphocyte blastogenic response [13]. It was shown that in some patients with malignant melanoma, the patient's emotional status (as well as tumor-host response factors such as mitotic rate and lymphocytic infiltration) could affect the prognosis [141. In conclusion, it appears that some of the newer concepts of NIM might enlarge research horizons and accelerate scientific discoveries. Chronobiology, immunopsychology and many other aspects of NIM appear to have attained a new degree of scientific legitimacy. NIM could well also expand horizons for the development of treatment and prevention strategies. The Second International Workshop on Neuroimmunomodulation (NIM) will be held June 1-6, 1986 in Dubrovnik, Yugoslavia. This meeting will be open. In addition, by invitation only, a satellite workshop titled NIM: Intervention in Aging and Cancer will follow on %11 June, 1986, in Stromboli, Sicily, Italy [15].
References
1. Proceedings of the First International Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, (in press); 'Neuroimmunomodulation',Gordon and Breach Science Publishers,
99
2. 3. 4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
New York (accepted for publication); Information regarding the above contact: N.H. Spector, FNP, NINCDS. NIH, Federal Building, Room 916, Bethesda, MD 20205, U.S.A. Blalock, J.E. and E.M. Smith, The immune system: our mobile brain?, Immunol. Today, 6 (4) (1985) 115-117. Kerza-Kwiatecki, A.P. and P.Y. Paterson, Neuroimmunomodulation Workshop Report, Clin. Immunol. Immunopathol., 1985, in press. Bulloch, K. and M.R. Cullen, A Comparative Study of the Autonomic Nervous System Innervation of the Thymus in the Mouse and Chicken (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Locke, S., L. Kraus, I. Kutz, S. Edbril, K. Phillips and H. Benson, Altered Natural Killer Cell Activity during Norepinephrine Infusion in Humans (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation, (NIM), IWGN, Bethesda, MD, 1985, in press. Kozlov, V.A. and V.V. Abramov, The Influence of Acetylcholine on the lgG Synthesis and Lymphocyte Proliferation In Vitro (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Solvason, H.B., V.K. Ghanta, R.N. Hiramoto and N.H. Spector, Augmentation of Host-Defense Response (Natural Killer Cell Activity) by a Conditioned Stimulus Only (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Hirsch, R. and K.P. Johnson, Placebo Induced Enhancement of Natural Killer Cell Activity in a Double Blind Trial of Recombinant Alpha 2 Interferon in Multiple Sclerosis Patients (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Wertman, E., H. Ovadia and O. Abramsky, Prevention of Experimental Autoimmune Disease by Anterior Hypothalamus Lesions in Rat (Abstract), First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Paterson, P.Y. and S.M. Harwin, In Vivo Cross Reactivity of Central Nervous System (CNS), Testes and Ovary Tissue Causes Two Types of CNS Lesions in Rat Sensitized to these Tissues (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Donahoe, R.M., J.J. Madden, F. Hollingsworth, D.A. Shafer, A. Falek, J.K.A. Nicholson and P. Bokos, Immunomodulation by Behaviorally Active Drugs Provides a Paradigm for Connecting AIDS-Like Processes and Psychoneuroimmunology (Abstract), Proc. First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Coe, C.L., L.T. Rosenberg and S. Levine, Immunological Consequences of Maternal Separation in Infant Primates (Abstract), First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Kelley, K.W., R. Dantzer and P. Mormede, The Role of Conditioning in Delayed-Type Hypersensitivity Immune Responses (Abstract), First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. Temoshok, L., R.W. Sagebiel and D.M. Sweet, Psychosocial Factors Associated with Tumor-Host Response in Cutaneous Malignant Melanoma (Abstract), First Int. Workshop on Neuroimmunomodulation (NIM), IWGN, Bethesda, MD, 1985, in press. For further information on the Dubrovnik meeting, contact Dr. B. Jankovic, Immunology Research Center, Vojvode Stepe 458, 11221 Belgrade, Yugoslavia, Telephone: (11) 467-465; and on the Stromboli meeting Dr. Walter Pierpaoli, Institute Integrative Biomedical Research, Lohwisstrasse 50, CH-8123 Ebmatingen, Switzerland, Telephone: 01-980-22-66.