The sense of smell is highly developed in rodents, and odors provide a critical set of stimuli that are necessary for reproduction, neuroendocrine responses and recognition of conspecifics, predators, and prey. We have shown that olfactory cues can also alter type 2 cytokine and antibody production following immunization with a protein antigen. This effect appears to be mediated by endogenous opioid production. The following specific aims have been designed to explore the role of endogenous opioids on immune function in our unique aNd naturalistic stress pheromone model. The central hypothesis is: Stress odor exposure (SOE) induces an endogenous opioid response that is immunomodulatory.
Specific Aim 1 : To test the hypothesis that type 2 cytokine production and immune effector functions in BALB/c mice immunized with KLH are preferentially altered by SOE via endogenous opioids.
Specific Aim 2 a: To test the hypothesis that the immunomodulatory effects of SOE may depend upon the antigen used to elicit the immune response.
Specific Aim 2 b: To test the hypothesis that administration of the opioid receptor antagonist naltrexone will abrogate SOE-induced changes in anti-HSV immunity.
Specific Aim 3 a: To determine whether endogenous opioid-induced changes in immune function are mediated centrally, resulting in an indirect effect on peripheral immune function, and/or peripherally, thereby directly affecting the immune system.
Specific Aim 3 b: To determine the specific class(es) of opioid receptors that are involved in stress odor-induced immune changes.
Specific Aim 4 : To determine if C57B1/6 mice, which do not have altered immune responses to KLH following stress odor exposure, have evidence of elevated endogenous opioids following odor exposure.
Lioy, Daniel T; Sheridan, Patricia A; Hurley, Sean D et al. (2006) Acute morphine exposure potentiates the development of HSV-1-induced encephalitis. J Neuroimmunol 172:9-17 |
Sheridan, Patricia A; Moynihan, Jan A (2005) Modulation of the innate immune response to HSV-1 following acute administration of morphine: role of hypothalamo-pituitary-adrenal axis. J Neuroimmunol 158:145-52 |