[Prolactin as pro-inflammatory cytokine--considerations on consolidated immunotherapy after high dosage therapy].
The pituitary hormone prolactin (PRL) is a proinflammatory cytokine, which cooperates with IL-2. Receptors of IL-2 (beta and gamma) and PRL belong to the same "Cytokine Growth Hormone Receptor Superfamily". PRL is necessary for IL-2 mediated activation and proliferation of T-cells and NK-cells and for LAK-cell generation, where optimal effects are found when low IL-2 levels are combined with PRL levels just above the upper normal range. IL-2 is currently investigated for NK and LAK enhancement after autologous haematopoetic stem-cell transplantation (STx) in order to reduce relapse rates. CONCLUSION 1: Drug-induced pulsatile PRL elevation (by metoclopramid) enhancing NK-LAK activity could be an easily feasible bridging therapy for the early posttransplant period, when Il-2 production is impaired and high-dose IL-2 therapy is precluded because of side effects. Low-dose cyclosporin A (Cy-A) after autologous STx induces an autologous graft versus host (GvH) and probably graft versus tumor (GvT) effect. On NK- and T-cells PRL interferes with Cy-A in two different, dose-dependent ways (subtherapeutical Cy-A increases PRL-binding to its receptor 4 fold; therapeutical Cy-A competes with PRL for binding in a dose dependent manner). Cy-A inhibits PRL-production on the transcriptional level in pituitary cells. In the thymus, which is a prerequisite for the development of autologous GvH, PRL and Cy-A are antagonists. CONCLUSION 2: It is not possible to predict the effect of prolactin elevation or reduction on the development of cyclosporin-A-induced autologous GVH as a means of reducing relapse after stem-cell transplantation.
Hinterberger-Fischer
M
M
Medizinische Abteilung, Donauspital im SMZ-Ost, Langobardenstrasse 122, A-1220 Wien. hinterberger@netway.at
D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D011388:Prolactin / Q000097:blood*
D007376:Interleukin-2; D016572:Cyclosporine; D011388:Prolactin