Metastatic-promoting effects of LPS: Sexual dimorphism and mediation by catecholamines and prostaglandins

Ranit Naor, Vered Domankevich, Shaily Shemer, Luba Sominsky, Ella Rosenne, Ben Levi, Shamgar Ben-Eliyahu

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammation is implicated in several medical conditions that are sexually dimorphic, including depression, cardiovascular diseases, autoimmunity, and presumably cancer progression. Here we studied the effects of the proinflammatory agent, LPS, on MADB106 lung tumor retention (LTR), and sought to elucidate underlying mechanisms and sexual dimorphism. F344 male and female rats were administered with LPS (0.001-1 mg/kg i.v.) simultaneously with tumor cell inoculation, and treated with a β-blocker (nadolol, 0.2-0.3 mg/kg s.c.), a COX inhibitor (indomethacin, 4 mg/kg s.c.) or both drugs. To study the role of NK cells, numbers and cytotoxicity of marginating-pulmonary NK cells were studied, and selective in vivo NK-depletion was employed. Serum levels of corticosterone, IL-6, and TNF-α were also assessed. The findings indicated that LPS increased LTR in both sexes, but 10-fold higher doses were needed in females to reach the increase evident in males. Additionally, nadolol and indomethacin reduced the effects of LPS, more so in males. In vivo NK-depletion and ex vivo NK activity studies suggested that LPS affected LTR through both NK-independent and NK-dependent mechanisms, the latter mediated through prostaglandin release in males. Corticosterone, IL-6, and TNF-α responses to LPS were sexually dimorphic, but were not associated with LPS or drugs' impacts on LTR. Overall, our findings demonstrate sexual dimorphism in LPS-induced elevated susceptibility to MADB106 experimental metastasis, and in potential humoral underlying mechanisms. Further studies are needed to elucidate additional immunological and non-immunological mediators of these dimorphisms, as well as to assess their involvement in other sexually dimorphic pathologies that are associated with inflammation.

Original languageEnglish
Pages (from-to)611-621
Number of pages11
JournalBrain, Behavior, and Immunity
Volume23
Issue number5
DOIs
StatePublished - Jul 2009

Keywords

  • Inflammation
  • LPS
  • Metastases
  • NK
  • Sex differences

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