EFFECTS OF PROLACTIN AND METOCLOPRAMIDE ON MACROPHAGE CYTOKINE GENE-EXPRESSION IN LATE SEPSIS

Previous studies indicate a profound suppression of tumour necrosis fa ctor alpha (TNF-alpha), IL-1 beta and IL-6 release capacity by periton eal macrophage (PM Phi), splenic macrophage (SM Phi) and Kupffer cells (KC) during late sepsis, Such a loss of functional capacity may reduc e the animal's ability to ward off infection, Prolactin is known to en hance monocyte, T- and B-lymphocyte immune responses under normal cond itions and has beneficial effects on cell-mediated immunity after haem orrhage, In this respect, the dopamine antagonist, metoclopramide, has been reported to increase circulating prolactin levels, Nonetheless, it remains unknown whether prolactin or metoclopramide have any saluta ry effect on macrophage (M Phi) cytokine gene expression following sep sis, To study this, male C3H/HeN mice were subjected to sepsis and imm ediately thereafter were treated with prolactin (100 mu g/25 g body we ight, s.c.), metoclopramide (100 mu g/100 g BW, s.c.) or given saline, PM Phi, SM Phi and KC (only SM Phi and KC in metoclopramide-treated a nimals) were isolated at 24 h after sepsis, The monolayers were stimul ated with or without LPS 10 mu g/ml for 1 h in vitro, Total RNA was ex tracted and mRNA was detected by semi-quantitative reverse transcripti on polymerase chain reaction (RT-PCR), A significant depression of con stitutive and inducible mRNA levels of IL-1 beta, IL-6 and TNF-alpha i n all three M Phi populations were observed, when compared with shams (with exception of KC IL-6 mRNA in unstimulated cells), Prolactin as w ell as metoclopramide treatment after the onset of sepsis caused signi ficant elevation of constitutive and inducible cytokine gene expressio n in all macrophages examined, Thus, prolactin and metoclopramide enha nce the depressed M Phi gene expression and may be useful in improving cell-mediated immunity during sepsis. (C) 1997 Academic Press Limited .