Macrophage-conditioned medium and interleukin 1 suppress vascular contractility

Area of Science:

• Immunology
• Physiology
• Pharmacology

Background:

• Sepsis can lead to significant alterations in vascular function.
• Mononuclear phagocytes, including macrophages, play a key role in the inflammatory response during sepsis.

Purpose of the Study:

• To investigate the effect of endotoxin-stimulated macrophages on rat aortic contractility.
• To identify potential mediators released by macrophages that affect vascular function.

Main Methods:

• Isolated rat aortas were incubated in medium conditioned by endotoxin-stimulated or nonstimulated macrophages.
• Aortic contractile responses to norepinephrine were measured.
• The effects of interleukin 1 and tumor necrosis factor on aortic contractility were assessed.
• Gel filtration was used to determine the molecular weight of suppressive factors.

Main Results:

• Medium conditioned by endotoxin-stimulated macrophages significantly reduced aortic contraction to norepinephrine.
• Endotoxin alone or medium from nonstimulated macrophages had no effect.
• Silica particle stimulation of macrophages in vivo also led to diminished aortic contractility.
• Interleukin 1 and tumor necrosis factor mimicked the suppressive effects of conditioned medium, with suppressive activity found at molecular weights corresponding to these cytokines.

Conclusions:

• Endotoxin-stimulated macrophages release factors, including interleukin 1 and tumor necrosis factor, that impair aortic contractility.
• Mononuclear phagocytes may contribute to sepsis-induced vascular dysfunction through the release of these cytokines.