**2.2 Mechanism of action of endotoxin**

Endotoxin involved in the activation of inflammatory genes by activating the TLR4 receptors along with their MD2 co-receptor, resulting the activation of NF-κB transcription with cytokines (TNFα, IL-6 and pro-IL-1β). The Lipopolysaccharide binding plasma protein transfers to membrane-bound CD14, as a result LPS transfer to TLR4. The intracellular lipopolysaccharide directly involved in the activation of murine caspase-4, 5 and 11 in humans, which in turn cleavage and activate caspase-1 and then to cleave pro-IL-1β. The activation of caspase-1 and 11 can cleave and activate the gasdermin D. This process allows the IL-1β to get out from plasma membrane and cell death by pyroptosis [7]. The other recognition receptors are TREM2 RAGE, the macrophage scavenger receptors and the β2 integrins (CD11a/CD18, CD11b/ CD18 and CD11c/CD18) may involve in the clearing of LPS and bacterial LPS in tissues and blood. This promotes the inflammation and toxicity (**Figure 2**) [8].

#### **2.3 Endotoxin entry in human body**

The huge amount of negative bacteria present in the gut of the body system. In sometime the gut edge leak or break down as a result gram negative bacteria and their endotoxin directly enter into the blood streams. This translocation is major reason for septic shock in seriously ill patients. This is known as endogenous endotoxin. Other way of entry is bacterial infection due to cyst and catheter or wound infection. The external source of endotoxin includes the polluted fluids or equipment. This is known as exogenous endotoxinsGram negative bacteria causes infection in intravenous infusion fluids resulted septicemia. Along with theses glassware used in IV therapy, cardiopulmonary bypass and dialysis equipment's also involved the endotoxin shock.

**Figure 2.** *Mechanism of action of endotoxin.*

After entry it causes pyrogen or can activate a number of signaling pathways of immuno competent cells that can cause to either swelling or programmed cell expire (apoptosis) of this cells. They are biologically essential even in the small amount [9].
