CCL2 as a trigger of manifestations of compensatory anti-inflammatory response syndrome in mice with severe systemic inflammatory response syndrome

Hitoshi Takahashi, Yasuhiro Tsuda, Makiko Kobayashi, David N. Herndon, Fujio Suzuki

Research output: Contribution to journalArticle

15 Scopus citations


Patients with compensatory anti-inflammatory response syndrome (CARS) are at a higher risk for infection with various opportunistic pathogens. CARS develops commonly in association with the manifestation of systemic inflammatory response syndrome (SIRS). In the present study, the role of SIRS-associated soluble factors on the CARS development was examined in mice with pancreatitis, a carrier of typical SIRS. Following the production of SIRS-related cytokines [tumor necrosis factor α and interleukin (IL)-1β], CC chemokine ligand 2 (CCL2), IL-4, and IL-10 (typical CARS cytokines) were detected in the sera of mice with pancreatitis. CCL2 has been described as an essential chemokine for the T helper cell type 2 manifestation. CARS effector cells (cells with an ability to produce IL-4 and IL-10) were not generated from normal T cells after stimulation with SIRS-related cytokines. However, these cells were generated from normal T cells after cultivation with peripheral blood neutrophils (PMN) from SIRS mice in a dual-chamber transwell. Normal T cells did not convert to CARS effector cells after transwell cultures with PMN from normal mice. CCL2 was detected in culture fluids of PMN from SIRS mice, and PMN from normal mice did not produce CCL2 into their culture fluids. CARS effector cells did not appear in PMN-depleted SIRS mice or SIRS mice treated with anti-CCL2 monoclonal antibody, and these cells were demonstrated in PMN-depleted SIRS mice after treatment with recombinant murine CCL2. These results indicate that CCL2 produced by PMN from SIRS mice is an active molecule on the SIRS-associated CARS manifestation.

Original languageEnglish (US)
Pages (from-to)789-796
Number of pages8
JournalJournal of Leukocyte Biology
Issue number4
StatePublished - Apr 1 2006



  • CARS
  • Neutrophils
  • SIRS

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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