From the Guidelines
Interleukins that activate the clotting system include primarily IL-1β, IL-6, and IL-8, as they promote coagulation through various mechanisms, including inducing tissue factor expression and suppressing natural anticoagulant mechanisms 1.
Key Interleukins Involved in Clotting System Activation
- IL-1β: Initiates self-perpetuating inflammatory responses, induces fever and vasodilation, and contributes to the activation of the clotting system 1.
- IL-6: Induces acute phase protein secretion, T and B cell growth and maturation, and increases fibrinogen production by the liver, enhancing clot formation 1.
- IL-8: Recruits neutrophils to the site of infection and activates platelets, promoting their aggregation and contributing to the clotting process 1.
Mechanisms of Clotting System Activation
The activation of the clotting system by these interleukins is multifactorial, involving the induction of tissue factor expression on endothelial cells and monocytes, the suppression of natural anticoagulant mechanisms, and the promotion of platelet activation and aggregation 1.
Clinical Implications
During inflammatory states such as sepsis or severe COVID-19, elevated levels of these interleukins can lead to a hypercoagulable state, potentially resulting in disseminated intravascular coagulation or thrombotic events 1. This connection between inflammation and coagulation explains why anti-inflammatory therapies may sometimes have anticoagulant effects and why inflammatory conditions often present with thrombotic complications.
From the Research
Interleukins and the Clotting System
- Interleukin-6 (IL-6) is a pro-inflammatory cytokine that plays a significant role in the human cytokine network 2.
- IL-6 signaling is mediated by building a complex of IL-6, the transmembrane IL-6 receptor (mIL-6R) or with soluble forms of IL-6R (sIL-6R), and the signal-transducing subunit molecule gp130 2.
- IL-6 has been shown to be involved in the regulation of essential cellular and humoral immune functions, and its dysregulation can result in inflammatory and autoimmune disorders as well as cancer development 2, 3.
- Elevated levels of IL-6 have been detected in patients with severe intra-abdominal sepsis, and higher levels of IL-6 at the onset of the sepsis syndrome correlated with a poor outcome 4.
- IL-6 has also been shown to be a prognostic indicator of outcome in severe intra-abdominal sepsis, with a sensitivity of 86.4% and a specificity of 78.9% in predicting mortality 4.
- In trauma patients, serum IL-6 levels have been shown to be significantly elevated in individuals with complications, such as inapparent hypoxia, fat embolism syndrome, sepsis, and multiple organ dysfunction syndrome 5.
- IL-6 has been proposed as a valuable biomarker for the early detection of trauma-related complications, with a high sensitivity and specificity at 24 hours post-trauma 5.
- Other interleukins, such as IL-1 alpha and beta, have also been shown to play a role in autoimmune and inflammatory disorders, and their deregulated signaling can cause devastating diseases manifested by severe acute or chronic inflammation 6.
Specific Interleukins Activating the Clotting System
- While the provided studies do not directly address the activation of the clotting system by interleukins, they do suggest that IL-6 and other interleukins play a role in inflammation and immune responses, which can indirectly affect the clotting system.
- Further research is needed to fully understand the relationship between interleukins and the clotting system.