@Dufresne Connections between the immune system and the kynurenine pathway are widely discussed in the literature. If the IDO metabolic trap exists, there must also be a causal chain of events that leads from the "trigger" event to springing the trap. Since many proposed ME/CFS triggers, especially viral infections, will up-regulate innate immunity, and since type I interferons are among the earliest host responses, I'm looking into the control of kynurenine pathway genes by interferons and other cytokines.
A physician at the 2019 Australia EMERGE meeting gave voice to the very reasonable idea that the cause of a chronic disease must be currently present in the body of the chronically ill patient. This could, of course, be true of ME/CFS, but it isn't the only possibility. The IDO metabolic trap is a bistability theory. It says that the cause of the disease was far in the past. The cause (or trigger) of the first crash pushed the patient beyond what the theoreticians call a "critical point." It's a trap in the sense that even though the trigger has been removed, the patient is still sick. What we measure in the blood or tissues will then consist only of effects. We will find causes of symptoms, and that will help, but what we really want is a cure. I can't point to another disease that works this way, so it often feels like I'm going far out on a thin limb. It's scientifically scary, but there are plenty of researchers looking for causes in their patient data, so it seems important to me and to some of my colleagues to follow this alternative hypothesis. Saying it might be a bistability disease doesn't, however, absolve me from the obligation to try to identify the causal trigger, and it's for that reason that I'm learning as much as I can about cytokines.
