title: Recombinant human prolactin improves antitumor effects of murine natural killer cells in vitro and in vivo.
abstract: OBJECTIVE
  To verify the effect of prolactin on natural killer (NK) cells in vivo and its implications for NK cell immunotherapy.
  
  
  METHODS
  Recombinant human prolactin (rhPRL; 30 microg, i.p.) was administered to BALB/c mice and severe combined immunodeficiency (SCID) mice 1 day before harvesting splenocytes for (51)Cr release assay to examine the effects of rhPRL on NK cells of normal mice. rhPRL (10 microg, i.p., every other day for a total of 5 injections) was administered to BALB/c mice after syngeneic bone marrow transplantation (SBMT) to determine its effects on NK cell reconstitution. CT26 tumor cells were injected into BALB/c mice intravenously on day 0, and interleukin (IL)-15-cocultured activated syngeneic NK cells (IL-15-NK) from SCID mice were intravenously injected into tumor-bearing BALB/c mice on day 1. The improvement of antimetastasis effects and survival of tumor-bearing mice by rhPRL were checked.
  
  
  RESULTS
  BALB/c and SCID mice receiving one rhPRL injection exhibited a significant increase in cellular cytotoxicity against YAC-1 target tumor cells; the specific lysis was enhanced from 12.5 to 17.3% in BALB/c mice and from 27.8 to 51.2% in SCID mice. BALB/c mice continuously receiving rhPRL injections exhibited significant increases in NK cell (DX5-positive) contents and cellularity in both the bone marrow and spleen in the SBMT model. The bone marrow NK cell contents were improved from 1.53 to 3.13% after rhPRL injection. NK cells from SCID mice were then cultured with recombinant human IL-15 (rhIL-15; 6000 IU/ml), rhPRL (10 ng/ml) or rhIL-15 plus rhPRL for 25 days. The cytotoxicity and cellularity were enhanced by rhPRL when tested on day 10, when comparing the rhIL-15 plus rhPRL group with the rhIL-15 group or rhPRL group, respectively. In the adoptive cellular immunotherapy study, the IL-15-NK plus IL-15 plus rhPRL group showed significantly lower numbers of lung metastases and longer survival than the IL-15-NK plus IL-15 group; the mean survival interval was prolonged from 31.5 to 53.7 days.
  
  
  CONCLUSIONS
  These results indicate that rhPRL is possibly an important regulator of NK cells and a potential biologic product for immunotherapy.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei City, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Ailing
authors.initials: A
authors.lastname: Li
authors.forename: Weici
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D019409:Interleukin-15 / Q000494:pharmacology / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011388:Prolactin / Q000494:pharmacology* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation
chemical_list: D019409:Interleukin-15; D011993:Recombinant Fusion Proteins; D011388:Prolactin