Prolactin regulates antitumor immune response through induction of tumoricidal macrophages and release of IL‐12

• Published in: International journal of cancer 2002-02, Vol.97 (4), p.493-500
• Main Authors: Majumder, Biswanath, Biswas, Ratna, Chattopadhyay, Utpala
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Adjuvants, Immunologic - physiology; Adjuvants, Immunologic - therapeutic use; Animals; Biological and medical sciences; Carcinoma, Ehrlich Tumor - drug therapy; Carcinoma, Ehrlich Tumor - immunology; Carcinoma, Ehrlich Tumor - pathology; Cells, Cultured - drug effects; Cells, Cultured - metabolism; Culture Media, Conditioned; Cytotoxicity, Immunologic - drug effects; Drug Synergism; Female; Host-tumor relations. Immunology. Biological markers; Humans; Inflammation; inflammatory macrophage; Interferon-gamma - pharmacology; interferon‐γ; Interleukin-12 - metabolism; interleukin‐12; Macrophage Activation - drug effects; Macrophages, Peritoneal - physiology; Medical sciences; Mice; Nitric Oxide - metabolism; Nitrites - metabolism; Phagocytosis; prolactin; Prolactin - pharmacology; Prolactin - physiology; Prolactin - therapeutic use; Recombinant Proteins; Superoxides - metabolism; Tumors; tumor‐associated macrophage
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.1624

The involvement of PRL in regulating monocyte/macrophage functions is suggested by the presence of PRL‐Rs in these cells. Here, we show that PRL, though it failed to activate mouse peritoneal resident macrophages (RMs), acted as a second signal and activated mouse peritoneal inflammatory macrophages (EMs) to a tumoricidal state. The cytotoxicity of mouse tumor‐associated macrophages (TAMs) isolated at day 1 of tumor (Ehrlich ascites carcinoma, EAC) growth was enhanced by PRL. However, with progression of tumor growth, TAMs became nonresponsive to the hormone. PRL‐induced killing of P815 target cells by EMs and TAMs was independent of TNF but correlated with the hormone‐induced augmentation of NO2− and O2− release in these macrophages. Administration of PRL in vivo inhibited EAC growth and augmented NO2− release by TAMs. PRL synergized with the TH1 cytokine IFN‐γ, a known activator of macrophages, in inducing tumor killing and release of NO2− from EMs and TAMs. The hormone might activate macrophages at least partially, through the release of IFN‐γ as anti‐IFN‐γ blocked IFN‐γ– as well as PRL‐induced cytotoxicity in EMs. The TH2 cytokine IL‐4 suppressed PRL‐induced activation of macrophages. PRL induced release of IL‐12 from EMs also, which suggested that the hormone might drive the TH1 response through IL‐12. Our observations further suggest that PRL alone and in synergy with IFN‐γ, released through induction of IL‐12, may generate tumoricidal macrophages and thus regulate the antitumor immune response of tumor hosts. © 2001 Wiley‐Liss, Inc.