TRAF6 can polyubiquitinate IKK-γ as well as itself, which recruits TGF-β activated kinase 1 (TAK1) in order to activate its ability to phosphorylate IKK-β. These pathways both work to degrade IKKγ, which releases NFκB and free it for translocation into the nucleus. Additionally, TAK1 can activate JNK to induce a MAP kinase pathway which leads to AP-1-induced gene expression. Together, AP-1 and NFκB lead to increased cytokine transcription, adhesion molecule production, and release of second messengers of infection. Central to all of these signalling pathways is the kinase IRAK4. Results show that IRAK4 is a crucial component in an animals response to IL-1. Animals deficient in this kinase were found to be lacking in the ability to recognize viral and bacterial invaders, and were completely resistant to lethal doses of lipopolysaccharide (LPS). This is due to IRAK4s function as both a structural protein and as a kinase. Both of these functions are required for the myddosome complex formation. Additionally, IRAK4 has been shown to be absolutely essential in a TLR signalling. IRAK4 deficient mice have a profoundly impaired ability to produce IL-6, TNF-α, and IL-12 in response to TLR ligands. However it is worthy of note that despite its importance to many immune signalling pathways, IRAK4 does not appear to be involved in TCR signalling. Clinical significance
There are three components of evidence that illustrate IRAK4s involvement in TLR signalling. First, IRAK4 is the initial kinase near the TLR receptor to activate downstream effectors such as cytokines and chemokines in the inflammatory cascade.
See Hs and Ts

Hypovolemia
Hypoxia
Hydrogen ions (Acidosis)
Hyperkalemia or Hypokalemia
Hypoglycemia
Hypothermia
Tablets or Toxins
Cardiac Tamponade
Tension pneumothorax
Thrombosis (e.g., myocardial infarction, pulmonary embolism)
Tachycardia
Trauma (e.g., hypovolemia from blood loss)The possible mechanisms by which the above conditions can cause pulseless in PEA are the same as those recognized as producing circulatory shock states. These are (1) impairment of cardiac filling, (2) impaired pumping effectiveness of the heart, (3) circulatory obstruction and (4) pathological vasodilation causing loss of vascular resistance and excess capacitance. More than one mechanism may be involved in any given case. Diagnosis
The absence of a pulse confirms a clinical diagnosis of cardiac arrest, but PEA can only be distinguished from other causes of cardiac arrest with a device capable of electrocardiography (ECG/EKG). In PEA, there is organised or semi-organised electrical activity in the heart as opposed to asystole (flatline) or to the disorganised  electrical activity of either ventricular fibrillation or ventricular tachycardia. Treatment
Cardiac resuscitation guidelines (ACLS/BCLS) advise that cardiopulmonary resuscitation should be initiated promptly to maintain cardiac output until the PEA can be corrected. The approach in treatment of PEA is to treat the underlying cause, if known (e.g. relieving a tension pneumothorax). Where an underlying cause for PEA cannot be determined and/or reversed, the treatment of pulseless electrical activity is similar to that for asystole.