>> Black Box Warning/RISK OF INFECTIONS <<
Mike Collins, at Bayer (Cutter Biological, Berkeley), demonstrated that passive admin. of anti-TNF led to an increased frequency of death in an experimental Listeria infection. This was using the Chiron antibody, in **1986**.
Mike had set up a number of in vivo assays for various bacterial pathogens. You handed him an antibody, and you got back data that was open and shut. His assays were reproducible to a ridiculous extent.
Fifteen years later, we've got the expected black box.
For those who might want to understand a bit about the mechanism...... inflammatory responses are generally good things. They protect you. Things can get out of hand (sepsis, rheumatoid arthritis, etc.), however.
If you give a ton of bacterial lipopolysaccharide to an experimental animal or human, you'll kill it.
If you give a little bit of lipopolysaccharide to an experimental animal and then challenge them later with the lethal dose, they can survive.
This is called endotoxin (lipopolysaccharide) tolerance.
Lipopolysaccharide induces a TNF response, and, no surprise, a little TNF can also protect against a lethal challenge with lipopolysaccharide.
One of the mediators of endotoxin tolerance is TNF.
Circular rationale...... if you take TNF (or cells that produce TNF) out of the system at the wrong time, you remove the protective response.
Thus..... while anti-TNF is highly effective for certain chronic inflammatory diseases, it can also disable an important element of innate immunity. |
