Maitham Khajah
Kuwait University, Kuwait
Title: The role of Granulocyte-macrophage colony stimulating factor (GM-CSF) in colitis
Biography
Biography: Maitham Khajah
Abstract
Background:
GM-CSF is a well-established priming agent and exerts proliferative effects for hematopoietic cells. Recent evidence suggests a potent chemotactic property towards neutrophils in vitro.
Aim:
To examine the role of GM-CSF in neutrophil recruitment to the colon in vivo and its effect on modulating colitis severity using the 2, 4, 6-trinitrobenzene sulphonic acid (TNBS) model in mice.
Methods:
Colitis was induced by a single intra rectal injection of TNBS (4mg, 20% ethanol) at day 1. Animals were treated with a single i.p injection of neutralizing anti-GM-CSF antibody (100 µg/mouse) on day 1, or multiple injections on day 1,2,3, and 4, and sacrificed on day 5 post-induction of colitis. Control mice were injected with i.p saline (vehicle) plus TNBS. On another experimental setup, colitis was induced in GMCSFRβ-/- and compared to wild type (WT) mice. Results: enhanced GM-CSF expression (at both gene and protein levels) was observed in colonic tissues at day 3 and 7 post colitis induction. A single injection of GM-CSF antibody did not modulate colitis severity, while multiple injections significantly reduced colonic MPO activity and colitis severity. In the GMCSFRβ-/- mice, colonic MPO activity was significantly reduced post colitis induction but no improvement in colitis severity was observed compared to WT mice.
Conclusion:
Anti-GM-CSF therapy significantly reduced neutrophil recruitment to the colon leading to reduced colitis severity.