Inhalative vs. systemic IL-10 administration: Differences in the systemic inflammatory response and end-organ inflammation following hemorrhagic shock

Interleukin-10 is known to modulate the systemic inflammatory response after trauma. This study investigates differences in the systemic and end-organ inflammation in animals treated with either inhalative or systemic IL-10 after experimental hemorrhagic shock (HS). Pressure controlled HS was performed in C57/BL6 mice for 1.5 h (6 animals per group). Inhalative or systemic recombinant mouse IL-10 (50 mu g/kg dissolved in 50 mu l PBS) was administered after resuscitation. Animals were sacrificed after 4.5 or 22.5 h of recovery. Serum levels of IL-6, IL-10, KC, MCP-1, and LBP were determined by ELISA. Pulmonary and liver inflammation was analyzed by standardized Myeloperoxidase (MPO) kits. Systemic and inhalative IL-10 administration affected the systemic inflammatory response as well as end-organ inflammation differently. Differences were obvious in the early (6 h) but not later (24 h) inflammatory phase. Systemic IL-10 application was associated with a decreased systemic inflammatory response as well as hepatic inflammation, whereas nebulized IL-10 solely reduced the pulmonary inflammation. Our study demonstrates that systemic and nebulized IL-10 administration differentially influenced the systemic cytokine response and end-organ inflammation. Early pulmonary but not hepatic protection appears to be possible by inhalative IL-10 application. Further studies are necessary to assess exact pathways. (C) 2012 Elsevier Ltd. All rights reserved.