Role of immune dysfunction in drug induced liver injury

Figure 1 Initiation of drug-induced liver injury - Direct damage by drug and metabolite. Drugs and their metabolites damage organelles and cell membrane of liver cells causing damage. ER: Endoplasmic reticulum.

Figure 2 Initiation of drug-induced liver injury - Indirect damage by drugs. Drugs can modulate the functioning of enzymes and transporters involved in drug metabolism and elimination that may lead to toxicity.

Figure 3 Immune allergic drug-induced liver injury. A: Endoplasmic reticulum stress by drug, causes misfolded protein resulting in cell death and release of stress signals and drug-protein complex. Kupffer cells ingest the drug-protein complex to T-helper cells; B: T-helper cells process it and present it to B-cells; C: B-cells produce anti-drug antibodies; D: These antibodies target the tissues, where drug is accumulated. KC: Kupffer cell; HSC: Hepatic stellate cells.

Figure 4 Mechanism of autoimmune drug-induced liver injury. A: Drug causes mitochondrial dysfunction resulting in cell death and release of HMGB-1 and other stress signals; B: Kupffer cells and Stellate cells get activated. Release cytokines, chemokines and toxins; C: Chemokines attract monocytes; D: Amplification of injury and cell death. KC: Kupffer cell; HSC: Hepatic stellate cells; ROS: Reactive oxygen species.