Prolactin is one of several hormones made by the pituitary gland. The main natural function of prolactin is to cause the breast to make milk in nursing mothers. While both men and women have prolactin in their blood, women possess significantly more in their circulation. Studies have demonstrated that prolactin exhibits a multitude of effects in the body besides its action on the breast including a positive action on the immune system. There have been a number of published studies demonstrating the stimulatory effects of prolactin on leukocyte function including potentiating neutrophil killing of bacteria and yeast, lymphocyte activation to specific antigens and immune stimuli, modulating cytokine production, enhancing natural killer cell activity, and augmenting antibody production. We are currently attempting to learn whether human prolactin, in collaboration with Johns Hopkins University, can be used to strengthen the innate immune system in healthy volunteers. A pharmokinetic study has been recently completed examining the optimal administration routes and toxicities associated with prolactin administration. Human prolactin is considered an experimental drug and is not approved by the U.S. Food and Drug Administration. The drug sponsor, Genzyme, has obtained permission from the U.S. Food and Drug Administration to investigate prolactin in a small number of humans. While no significant alterations in innate immune parameters were observed, the small cohort of subjects made such determinations difficult. Age-associated changes in immune function in humans and animals are quite important with regard not only to the general health of aged persons but also to the general features of the immune system itself. Elderly subjects have been shown to be more susceptible to viral and bacterial infections and are believed to be more susceptible to cancer. There have been a number of hypotheses for the diminished immune responses observed in elderly subjects including involution of the thymus, active immunosuppression, replication senescence of immune cells, cellular signaling defects, and alterations in cytokine expression profiles. A series of clinical studies have revealed that elderly subject, in contrast to their younger counterparts, exhibit poor cellular and humoral immune responses to vaccines even in the presence of standard adjuvants. Currently, many laboratories are focusing their research efforts into developing more effective adjuvants for use in elderly populations. Our laboratory in collaboration with various investigators at the National Cancer Institute has demonstrated that prolactin potentiates human and rodent lymphocyte activation and proliferation in response to various antigens and stimuli both in vitro and in vivo. Efforts are current underway to initiate a larger prolactin infusion study in young and older subjects to examine its role as an immunoadjuvant. It is our hope to examine the effects of recombinant human prolactin to strengthen the immune system in healthy individuals in response to vaccines to common pathogens including pneumococcus and influenza. The primary objectives of this clinical study will be to determine if prolactin administration in combination with known immunogens, in particular influenza and pneumococcal vaccines, can potentiate cellular and humoral responses in elderly subjects. Whole blood will be drawn prior to and post- vaccine and prolactin administration for biological and blood chemistry assessments as well as for specimen banking. All serum samples will be assayed for the presence of total immunoglobulin as well as the presence of vaccine antigen-specific antibodies. Peripheral blood mononuclear cells will be examined for vaccine antigen-specific proliferation and cytotoxic T cell activity. In addition, activated cells will be assessed for various growth factors to assess the effects of prolactin on cellular activation and differentiation. In this way, we should be able to assess both the in vitro and in vivo alterations induced by prolactin. - Prolactin, Growth-Hormone, Immunosenesence, Immune-Monitoring

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000758-02
Application #
6288748
Study Section
Special Emphasis Panel (LI)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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