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Int J Cancer. 2002 Feb 1;97(4):493-500.

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

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1
Department of Immunoregulation and Immunodiagnosis, Chittaranjan National Cancer Institute, Kolkata, India.

Abstract

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-gamma, 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-gamma as anti-IFN-gamma blocked IFN-gamma- 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-gamma, released through induction of IL-12, may generate tumoricidal macrophages and thus regulate the antitumor immune response of tumor hosts.

PMID:
11802212
DOI:
10.1002/ijc.1624
[Indexed for MEDLINE]
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