PROLACTIN MODULATION OF NITRIC-OXIDE AND TNF-ALPHA PRODUCTION BY PERIPHERAL NEUTROPHILS IN RATS

It has been demonstrated that prolactin (PRL) is a potent immunomodula tor that exerts stimulatory effects on physiological responses of immu ne cells. In the present research we have investigated whether PRL may influence nitric oxide (NO) and/or tumor necrosis factor-alpha (TNF-a lpha) production in neutrophils obtained from inflammatory exudate of carrageenin-induced experimental pleurisy in the rat. In this acute mo del of inflammation the role of endogenous NO was evaluated using an i nhibitor of NO-synthase, N-G-nitro-L-arginine methyl ester (L-NAME). A treatment of animals with L-NAME (10 mg/kg s.c.) induced a reduction of volume and cell number of pleural exudate and a decrease of nitrite production (measured by the Griees reaction) by polymorphonuclear cel ls after 24 h of incubation, while D-NAME, the inactive isomer, was wi thout effect. Neutrophils from ovine prolactin (oPRL) treated rats (5 mg/kg for 5 times s.c.) or from rats with a hyperprolactinaemia induce d by pituitary gland graft produced higher amounts of NO both after 24 and 48 h of incubation. On the contrary, a clear reduction in the pro duction of NO was found in neutrophils from rats treated with bromocri ptine (BRC) (2 mg/kg s.c.), a dopamine D-2-receptor agonist. TNF-alpha production (measured by MTT/cytotoxic assay) by neutrophils was marke dly increased in PRL-treated or pituitary-grafted rats in comparison t o controls, whereas BRC treatment reduced TNF-alpha production.