Interleukin-10 suppresses natural killer cell but not natural killer T cell activation during bacterial infection

• Published in: Cytokine (Philadelphia, Pa.) Vol. 33; no. 2; pp. 79 - 86
• Main Authors: Scott, Melanie J., Hoth, J. Jason, Turina, Matthias, Woods, Dustin R., Cheadle, William G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 21.01.2006
• Subjects: Animals; Bacterial Infections - immunology; CD69; Interferon gamma; Interleukin-10 - immunology; Interleukin-10 - metabolism; Interleukin-12 - immunology; Interleukin-12 - metabolism; Interleukin-18 - immunology; Interleukin-18 - metabolism; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lymphocyte; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Peritonitis; Sepsis; Time Factors; Sepsis; CD69; Lymphocyte; Peritonitis; Interferon gamma
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2005.12.002

Interleukin (IL)-10 is an anti-inflammatory cytokine known to modulate the outcome of sepsis by decreasing pro-inflammatory cytokine production, including IL-12, a main activator of natural killer (NK) cells. We hypothesized that neutralization of IL-10 would increase NK and natural killer T (NKT) cell activation through increased IL-12 in a mouse model of bacterial peritonitis. NK and NKT cell activations were measured by CD69 expression on NK1.1+/CD3− and NK1.1+/CD3+ cells after cecal ligation and puncture (CLP). NK cells were significantly more activated in mice treated with anti-IL-10 antibodies, whereas no such effect was observed in NKT cells. Similarly, intracellular interferon gamma (IFN-γ) levels were increased in NK cells of anti-IL-10-treated mice, but not in NKT cells. IL-12 and IL-18 levels were increased in both CLP groups, but in anti-IL-10-treated mice, early IL-12 and late IL-18 levels were significantly higher than in controls. Survival at 18 h after CLP was lower in anti-IL-10 mice, which was associated with increased liver neutrophil accumulation. In summary, these data show an activating effect of IL-10 on NK, but not on NKT cells after CLP, which corresponded with decreased survival, higher IFN-γ production, and increased remote organ neutrophil accumulation. These effects were not mediated by IL-12 and IL-18 alone, and reinforce a role for NK cells in remote organ dysfunction following peritonitis.