PROLACTIN ADMINISTRATION FOLLOWING HEMORRHAGIC-SHOCK IMPROVES MACROPHAGE CYTOKINE RELEASE CAPACITY AND DECREASES MORTALITY FROM SUBSEQUENT SEPSIS

Although prolactin is reported to counteract the immunosuppressive eff ects of glucocorticoids, cyclosporine, and morphine, it remains unknow n whether prolactin has any salutary effects on the depressed immune r esponses following severe hemorrhage, To study this, mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 min, th en adequately resuscitated and divided into two groups, One group rece ived saline vehicle, while the other group received prolactin (100 mu g/25 g body weight, s.c.) immediately before resuscitation, Two hours thereafter, peritoneal (pM phi) and splenic macrophages (sM phi) were harvested and assessed not only for their ability to release IL-1 and IL-6, but also for cytokine gene expression using semiquantitative rev erse transcription and PCR, In an additional group, mice were subjecte d to sepsis by cecal ligation and puncture 3 days after hemorrhage, He morrhage markedly decreased the ability of pM phi and sM phi to releas e IL-1 and IL-6, This was, however, associated with increased mRNA exp ression for IL-1 beta and IL-6 and increased serum corticosterone leve ls, Following prolactin treatment of hemorrhaged mice, IL-1 beta and I L-6 mRNA levels as well as cytokine release capacity and blood cortico sterone levels were comparable to the values in sham animals, Prolacti n also improved the survival of animals subjected to sepsis after hemo rrhage, Thus, the immunosuppression following hemorrhage appears to be mediated and modulated by hormones from the hypothalamic-pituitary-ad renal axis. Furthermore, prolactin represents a novel immunomodulating hormone for the treatment of immunodepression encountered after hemor rhagic shock and for decreasing the mortality from subsequent sepsis u nder those conditions.