Cytokines are systemic effectors of lymphatic function in acute inflammation

Area of Science:

• Immunology
• Physiology
• Vascular Biology

Background:

• The lymphatic system's role in inflammation and infection is not fully understood.
• Lymphatic vessels are crucial for immune cell transport and fluid balance.

Purpose of the Study:

• To investigate the impact of acute inflammatory insult on lymphatic propulsion.
• To identify specific cytokines involved in lymphatic dysfunction during inflammation.

Main Methods:

• Near-infrared fluorescence (NIRF) imaging to noninvasively assess lymphatic propulsive function in mice.
• Administration of lipopolysaccharide (LPS) to induce inflammation.
• Intradermal injection of cytokines (IL-1β, TNF-α, IL-6) and nitric oxide synthase inhibitor (L-NIL).

Main Results:

• LPS injection caused rapid, systemic cessation of lymphatic pumping within 4 hours.
• Elevated serum cytokines (IL-1β, TNF-α, IL-6) correlated with lymphatic pumping cessation.
• Intradermal IL-1β, TNF-α, and IL-6 decreased lymphatic pulsing frequency and velocity.
• IL-1β induced contralateral lymphatic vessel dilation and leakiness.
• L-NIL pre-treatment mitigated IL-1β's effects on lymphatic pumping.

Conclusions:

• Acute inflammatory insults lead to rapid, systemic impairment of lymphatic propulsion.
• Cytokines, particularly IL-1β, act as key mediators of lymphatic pumping cessation.
• Nitric oxide pathways are implicated in the cytokine-mediated dysfunction of lymphatic vessels.