The goal of the proposed research is to better understand the physiological consequences of stress or handling as these are reflected in alterations of different parameters of antibody and cell-I mediated immune responses to levels of antigenic stimulation that are more characteristic of the stimulation that occurs under natural conditions. To this end, we have proposed descriptive parametric studies to examine the development of secondary (memory) immune responses generated following low dose antigen priming in footshock stressed, handled, and control mice. We will also determine whether there are differential effects of stress on primary and secondary antibody responses in normal versus immunologically compromised (i.e., immunosuppressed) mice. Further studies, predicated on these data, will determine whether the animal's ability to predict or control the stressor alters its immunomodulatory effects and whether stress-induced changes in immunity can be conditioned. The effects of handling and footshock stress (and the degree to which the animal is capable of coping with stress) on the metastatic spread of the Line I tumor will also be studied in relation to the immunologic changes induced by these forms of stimulation. Using both in vitro and in vivo protocols, several possible mechanisms that might underlie the immunomodulatory effects of handling and footshock that have already been observed and that will be uncovered in the proposed studies will also be explored. Data from our proposed studies may be clinically relevant in situations where patients are immunosuppressive by human immunodeficiency disease (HIV) or receive immunosuppressive drugs as part of a chemotherapeutic protocol or in association with organ transplantation. These basic studies will also meet the defined need to characterize the range and parameters of immune function that are subject to the influence of environmental (e.g ., """"""""stress"""""""") conditions and will enable a more focused approach to the neuroendocrine and immunologic mechanisms underlying the effects of stress on immunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH045681-01
Application #
3385497
Study Section
MH Acquired Immunodeficiency Syndrome Research Review Committee (MHAZ)
Project Start
1989-09-01
Project End
1992-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
School of Medicine & Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Moynihan, J A; Karp, J D; Cohen, N et al. (2000) Immune deviation following stress odor exposure: role of endogenous opioids. J Neuroimmunol 102:145-53
Moynihan, J A; Callahan, T A; Kelley, S P et al. (1998) Adrenal hormone modulation of type 1 and type 2 cytokine production by spleen cells: dexamethasone and dehydroepiandrosterone suppress interleukin-2, interleukin-4, and interferon-gamma production in vitro. Cell Immunol 184:58-64
Felten, S Y; Madden, K S; Bellinger, D L et al. (1998) The role of the sympathetic nervous system in the modulation of immune responses. Adv Pharmacol 42:583-7
Kruszewska, B; Felten, D L; Stevens, S Y et al. (1998) Sympathectomy-induced immune changes are not abrogated by the glucocorticoid receptor blocker RU-486. Brain Behav Immun 12:181-200
Moynihan, J A; Kruszewska, B; Brenner, G J et al. (1998) Neural, endocrine, and immune system interactions. Relevance for health and disease. Adv Exp Med Biol 438:541-9
Callahan, T A; Moynihan, J A; Piekut, D T (1998) Central nervous system activation following peripheral chemical sympathectomy: implications for neural-immune interactions. Brain Behav Immun 12:230-41
Brenner, G J; Moynihan, J A (1997) Stressor-induced alterations in immune response and viral clearance following infection with herpes simplex virus-type 1 in BALB/c and C57B1/6 mice. Brain Behav Immun 11:9-23
Moynihan, J A; Ader, R (1996) Psychoneuroimmunology: animal models of disease. Psychosom Med 58:546-58
Kruszewska, B; Felten, S Y; Moynihan, J A (1995) Alterations in cytokine and antibody production following chemical sympathectomy in two strains of mice. J Immunol 155:4613-20
Brenner, G J; Cohen, N; Moynihan, J A (1994) Similar immune response to nonlethal infection with herpes simplex virus-1 in sensitive (BALB/c) and resistant (C57BL/6) strains of mice. Cell Immunol 157:510-24

Showing the most recent 10 out of 19 publications