Prolactin Is an Antagonist of TGF-β Activity and Promotes Proliferation of Murine B Cell Hybridomas

Abstract

Prolactin (PRL) is an immunomodulator that has been demonstrated to enhance immune responses bothin vitroandin vivo.Prolactin enhances the proliferative response of lymphoid cells to both nonspecific mitogens and specific antigens and increases their production of IL-2 and interferon-γ. Studies were performed to examine whether recombinant human prolactin (r-hPRL) also acts as a growth factor for B cell hybridomas. Prolactin was able to stimulate proliferation of murine B cell hybridomas in a dose-dependent manner and enhanced their proliferation in response to IL-4, IL-5, and IL-6. This increase in proliferation resulted in an overall increase in antibody production. Studies were also undertaken to examine the effect of PRL with transforming growth factor β (TGF-β), an immunosuppressive cytokine. Hybridoma cell lines incubated with TGF-β demonstrated a dose-dependent decrease in proliferation. Variability in the degree of inhibition was observed among the various hybridomas in their responsiveness to TGF-β. The addition of r-hPRL to the cultures reversed the anti-proliferative effects of TGF-β. The mechanism by which PRL can overcome the anti-proliferative effect of TGF-β is under investigation. These findings provide an additional rationale for using r-hPRL clinically in immunosuppressed patients in certain disease settings such as AIDS and cancer, where overexpression of TGF-β has been implicated in disease development and progression.