GM-CSF counteracts hemorrhage-induced suppression of cytokine-producing capacity

To study whether a treatment with the hematopoietic growth factor GM-CSF restores the attenuated ex-vivo cytokine-producing capacity of macrophages after sublethal hemorrhagic shock.

Male Sprague-Dawley rats.

20 microg/animal of recombinant murine GM-CSF after shock via arterial line.

Hemorrhagic shock was established by pressure-controlled bleeding to a mean arterial pressure of 50 mm Hg for 35-40 min and consecutive resuscitation. 24 h after hemorrhage, lipopolysaccharide (LPS)-induced cytokine production of isolated macrophages derived from different compartments was measured.

A significant reduction of LPS-induced TNFalpha production was found in whole blood cultures (1.0 +/- 0.7 ng/ml after sham vs. 0.23 +/- 0.08 ng/ml after shock operation), macrophages derived from spleen (0.88 +/- 0.23 ng/ml after sham vs. 0.03 +/- 0.1 ng/ml after shock operation), peritoneum (2.2 +/- 0.7 ng/ml after sham vs. 0.29 +/- 0.4 ng/ml after shock operation) and bronchoalveolar fluid (0.65 +/- 0.13 ng/ml after sham vs. 0.003 +/- 0.027 ng/ml after shock operation, mean +/- S.D.). In cells from animals treated with GM-CSF a significantly enhanced LPS-induced TNFalpha production in splenic, alveolar and peritoneal macrophages was found after shock compared to the cells derived from untreated animals (peritoneum: 289 +/- 366 ng/ml TNFalpha after shock vs. 2066 +/- 94 ng/ml TNFalpha after shock and GM-CSF; lung: 9 +/- 12 ng/ml TNFalpha after shock vs. 64 +/- 17 ng/ml TNFalpha after shock and GM-CSF; spleen: 58 +/- 96 ng/ml TNFalpha after shock vs. 548 +/- 47 ng/ml TNFalpha after shock and GM-CSF). Blood cultures collected from rats after hemorrhagic shock did not show a significant increase of TNFalpha-production after GM-CSF treatment.

Hemorrhagic shock caused a depression of the TNFalphaa response to LPS which was partly counteracted by treatment with GM-CSF. Therefore, GM-CSF represents a promising approach to normalise trauma- and shock-induced immune dysfunction.