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Up-regulation of prolactin gene expression and feedback modulation of lymphocyte proliferation during acute allograft
G K Shen1, D W Montgomery, E D Ulrich
1Research Service, Veteran's Affairs Medical Center, Tuscon, Ariz.
Background:
Although recent evidence suggests that prolactin is important in the immune response, bidirectional communication between prolactin and the immune system has not been demonstrated previously. We examined our hypothesis that this communication exists during mouse skin allograft rejection.
Methods:
Serum prolactin levels were measured by bioassay, and pituitary prolactin mRNA was examined by use of Northern blots, in BALB/c mice receiving skin allografts from C57BL mice, on days 2, 4, and 6 after grafting. The feedback effects of prolactin on splenic lymphocytes were assessed in one-way mixed lymphocyte reactions, with or without added interleukin-2 (IL-2) or IL-4.
Results:
Prolactin mRNA was increased significantly in grafted animals compared with sham animals (2.4-fold by day 4). Serum prolactin bioactivity was also elevated on all days tested. Prolactin treatment resulted in dose-dependent modulation of the mixed lymphocyte reaction with lymphocytes from grafted animals but not from sham animals. These effects depended on the time points and the presence of IL-2 or IL-4; the maximal enhancement occurred with day-4 lymphocytes cultured with IL-4 (80%).
Conclusions:
This report is the first to implicate in vivo immune regulation of prolactin gene expression. Our observations indicate that bidirectional interaction exists between prolactin and the immune system and provide a rationale for altering prolactin levels to treat allograft rejection.