TY - JOUR
T1 - The role of interleukin-10 in the regulation of the systemic inflammatory response following trauma-hemorrhage
AU - Schneider, Christian P.
AU - Schwacha, Martin G.
AU - Chaudry, Irshad H.
N1 - Funding Information:
This work was support by USPHS Grant GM37127 to IHC. Dr. Schwacha is a recipient of an NIH Independent Scientist Award, K02 AI049960.
PY - 2004/5/24
Y1 - 2004/5/24
N2 - Pro-inflammatory cytokine release after shock is central in the development of subsequent multiple organ dysfunction syndrome. Some studies suggest that interleukin-10 (IL-10) is an immunosuppressive mediator after injury or sepsis, while others suggest that IL-10 is an important regulator of the pro-inflammatory response. We hypothesized that in a model of trauma and hemorrhagic shock (TH), IL-10 regulates pro-inflammatory cytokine activity via an autocrine effect on cytokine mRNA transcription in Kupffer cells early after TH. To study this, male C3H/HeN mice were sham-operated or subjected to TH. Plasma levels of TNF-α, IL-6 and PGE2 were elevated following TH. A sharp peak in IL-10 levels was observed at 2 h after the insult. Kupffer cell (KC) depletion prior to TH reduced plasma IL-6, IL-10 and TNF-α levels, whereas treatment with anti-IL-10 after TH increased IL-6 and TNF-α levels. Kupffer cell mRNA expression for IL-6, IL-10 and TNF-α was elevated in the TH group and further increased by anti-IL-10 treatment. These findings indicate that KC-dependent IL-10 regulates the early systemic inflammatory response after TH. Thus, while IL-10 is an important mediator of immunosuppression following traumatic injury, it also is beneficial with regard to its ability to counter-regulate the early inflammatory response under such conditions.
AB - Pro-inflammatory cytokine release after shock is central in the development of subsequent multiple organ dysfunction syndrome. Some studies suggest that interleukin-10 (IL-10) is an immunosuppressive mediator after injury or sepsis, while others suggest that IL-10 is an important regulator of the pro-inflammatory response. We hypothesized that in a model of trauma and hemorrhagic shock (TH), IL-10 regulates pro-inflammatory cytokine activity via an autocrine effect on cytokine mRNA transcription in Kupffer cells early after TH. To study this, male C3H/HeN mice were sham-operated or subjected to TH. Plasma levels of TNF-α, IL-6 and PGE2 were elevated following TH. A sharp peak in IL-10 levels was observed at 2 h after the insult. Kupffer cell (KC) depletion prior to TH reduced plasma IL-6, IL-10 and TNF-α levels, whereas treatment with anti-IL-10 after TH increased IL-6 and TNF-α levels. Kupffer cell mRNA expression for IL-6, IL-10 and TNF-α was elevated in the TH group and further increased by anti-IL-10 treatment. These findings indicate that KC-dependent IL-10 regulates the early systemic inflammatory response after TH. Thus, while IL-10 is an important mediator of immunosuppression following traumatic injury, it also is beneficial with regard to its ability to counter-regulate the early inflammatory response under such conditions.
KW - Anti-IL-10
KW - Cytokine
KW - GdCl
KW - Immune response
KW - Kupffer cell
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U2 - 10.1016/j.bbadis.2004.01.003
DO - 10.1016/j.bbadis.2004.01.003
M3 - Article
C2 - 15158910
AN - SCOPUS:2442666254
VL - 1689
SP - 22
EP - 32
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 1
ER -