A Th1-Type Cytokine Named Prolactin. Facts and Hypotheses

Abstract

Evidence supporting the role of PRL as a Th1-type cytokine and its potential therapeutic implications in human immunodeficiency virus (HIV) infection, graft-versus-host disease (GVHD), chronic hepatitis C (CHC) and preeclampsia is reviewed. In patients with HIV infection, dopaminergic adaptive mechanisms maintain PRL at a high but physiological con- centration, which stimulates CD4 + T lymphocyte proliferation and increases viral apoptosis attempting to survive. In patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation complicated by chronic GVHD, the dopaminergic adaptive mechanisms tend to decrease the high normal serum PRL concentrations. On the contrary, in transplan- tations complicated by acute GVHD, donors with a Th1 cytokine profile may be prone to induce acute GVHD in their recipients, but a mild sustained rise in PRL concentrations after transplantation in these patients may reduce the severity of the disease. In patients with CHC, mild, drug-induced hyperprolactinemia is associated with increased peripheral lymphocytes and natural killer cell cytotoxicity that induces apoptosis in the infected hepatocytes. In early pregnancy, endogenous low-molecular-weight PRL (14-16 kDa) may act as a Th1-cytokine participating in the faulty trophoblastic invasion of the placenta in women with subse- quent severe preeclampsia. In conclusion, PRL may participate as an important immunoregulatory factor in the pathophysiology of HIV infection, GVHD, CHC and preeclampsia through its Th1-type cytokine-like actions.