PROLACTIN IS AN ANTAGONIST OF TGF-BETA ACTIVITY AND PROMOTES PROLIFERATION OF MURINE B-CELL HYBRIDOMAS

Prolactin (PRL) is an immunomodulator that has been demonstrated to en hance immune responses both in vitro and in vivo. Prolactin enhances t he proliferative response of lymphoid cells to both nonspecific mitoge ns and specific antigens and increases their production of IL-2 and in terferon-gamma. Studies were performed to examine whether recombinant human prolactin (r-hPRL) also acts as a growth factor for B cell hybri domas, 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 r esulted in an overall increase in antibody production. Studies were al so undertaken to examine the effect of PRL with transforming growth fa ctor beta (TGF-beta), an immunosuppressive cytokine, Hybridoma cell li nes incubated with TGF-beta demonstrated a dose-dependent decrease in proliferation. Variability in the degree of inhibition was observed am ong the various hybridomas in their responsiveness to TGF-beta. The ad dition of r-hPRL to the cultures reversed the antiproliferative effect s of TGF-beta. The mechanism by which PRL can overcome the anti-prolif erative effect of TGF-beta is under investigation. These findings prov ide an additional rationale for using r-hPRL clinically in immunosuppr essed patients in certain disease settings such as AIDS and cancer, wh ere overexpression of TGF-beta has been implicated in disease developm ent and progression. (C) 1998 Academic Press.