Immune-mediated injury, mechanisms

Possible mechanisms of fenofibrate-induced liver injury include activation of peroxisome proliferation-activator receptors, a hypersensitivity reaction, and immune -mediated injury from cross-reactivity of the drug with autoantigens. The authors referred to six reported cases of hepatic fibrosis attributed to fenofibrate. Raised transaminase activities occur commonly with fenofibrate but are generally transient, reverse on withdrawal, and do not result in long-term injury. Fenofibrate should be withdrawn if higher than normal enzyme activities persist, and a liver biopsy should be considered if liver enzymes do not normalize after withdrawal. 

The different types of immune-mediated injury are not mutually exclusive. More than one hypersensitivity mechanism may be involved in the response to a particular antigen. Also the resulting pathology, particularly that caused by type III and IV, reactions may appear very similar, although the mechanisms leading to the effect are different. 

Classification of Immune-Mediated Injury Based on Mechanisms... 

Drugs can cause fiver injury by a number of mechanisms, but the most common is idiosyncratic, immune-mediated injury to hepatocytes, characterized by elevations in... 

This case of heroin myelopathy is similar to other reported cases, except that this case occurred with intranasal rather than intravenous use. The MRI findings were consistent with a transverse myelitis. The authors suggested that hypersensitivity and an immune-mediated attack on the spinal cord was the likely mechanism of injury. 

The fact that immunosuppressant therapy has not been proven to halt progression has been cited as evidence against an immune-mediated mechanism of motor neuron injury. However, several potential explanations for this lack of efficacy could exist. Immune suppression may be too little and too late. By the time symptoms and signs appear, extensive CNS damage may already have occurred due to increased calcium and free radicals, and it may be difficult to stop the process that the immune reactivity initiated. Further, immunosuppression therapies may not adequately access the CNS and... 

FIGURE 47-3. The major pathways of immune-mediated glomerular injury. Mechanisms 1 and 2 primarily acton the glomerular epithelial cell and result in noninflammatory lesions. Mechanisms 3 and 4 involve participation of effector cells and result in glomerular inflammation and structural damage. (Adapted from Couser. )... 

Two major types of mechanisms have been proposed to account for DILL The first mechanism involves the intrinsic hepatotoxicity of a particular drug itself or, more frequently, a result of the toxic effects of its metabolites on vital cellular targets of the liver. The second mechanism reflects an immune-mediated reaction culminating in hepatic inflammation and injury. 

Altered mental status is a pre-requisite for the diagnosis of acute disseminated encephalomyelitis (ADEM), often a consequence of non-CNS infection or immunization (Tenembaum et al., 2007) The disorder is the subject of a complete chapter in this book, so this discussion wiU be limited to the mechanisms of brain injury as it pertains to encephalopathies mediated by brain inflammation. There is excellent evidence to suggest that the brain injury is primarily immune mediated and therefore inflammatory in nature. Antigenic similarities between the viral antigens... 

Adams DH, Ju C, Ramaiah SK, Uetiecht J, Jaeschke H (2010) Mechanisms of immune-mediated hver injury. Toxicol Sci, 115, 307-21. 

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