NF-kB, more formally known as nuclear factor-kappaB, is the Master Switch controlling inflammation.

[stextbox id="grey"]You don’t need to know anything about NF-kB – or how it works – except that it is the inflammation Master Switch, and that activating NF-kB turns inflammation processes on, while inhibiting NF-kB turns inflammation processes off. Nonetheless, a brief description follows. [/stextbox]

Click on any picture to see a larger version.

NF-kB is a transcription factor. Meaning it is a protein that controls when genes are turned on or off. When genes are turned on they produce proteins. In the case of NF-kB these proteins control inflammation.

NF-kB is in fact the Master Switch – the primary means by which inflammation is ‘adjusted’ – turned on and off. Many different molecules interact with NF-kB – some stimulating it (increasing inflammation) and others inhibiting it (decreasing inflammation.) The balance between these positive (pro-inflammatory) and negative (anti-inflammatory) influences determines the extent of inflammation at any given time.

(Click the picture below to enlarge)

NF-kB is the Master Switch because it turns on – or not – the genes that code for mediators of  inflammation (inflammation stimulants.)

NF-kB activation leads to inflammation, and without NF-kB activation, there is no inflammation.

To ‘turn on’ the genes for inflammation, NF-kB must move from the cytoplasm to the nucleus.

Constant inflammation is avoided because, in its usual state, NF-kB is bound to an inhibitor that keeps it in the cytoplasm and prevents it from entering the nucleus. The inhibitor is known as IkB (Inhibitor of k-B.)

A kinase known as IKK (a kinase cuts) frees the k-B from the inhibitor that held it in the cytoplasm – so NF-kB may now enter the nucleus where it binds with genes and ‘turns on’ inflammation. (Click the picture below to enlarge.)

The immune system is extremely complicated when you try to follow the intricacies of hundreds of different pathways and mediators that are known – with more being discovered each week. But like any well-designed system, there is a central point of control.

Instead of thinking “body” (or cell) and “inflammation” let’s imagine a “building” and consider “temperature”- we just want to turn down the heat a bit.

Granted, this is a very high-tech building with a very complex heating system. So there are wires (pathways) running everywhere, and hundreds of sensors (cells) with different functions, providing feedback (cytokines and other mediators of inflammation) on temperature, airflow, humidity – even sensing the amount of dust or the presence of certain chemicals.

One way to adjust the temperature might be to try and figure out each small detail of the entire system. Then perhaps we could tweak various components as a means of cooling off. But that might take a while – and we might not get it right.

I suggest a better plan would be to try adjusting the thermostat: NF-kB. One of the reasons we know NF-kB is the thermostat – the Master Switch – is that as we follow the various ‘wires’ (pathways) controlling inflammation, they invariably lead us to NF-kB.

In fact most treatments for inflammation work by influencing NF-kB. Aspirin, steroids (corticosteroids,) and many natural substances exert their anti-inflammatory effect, at least in part, through direct interaction with the Master Switch: NF-kB. It seems the extent to which they act on NF-kB determines how effective they are, while their effects on other parts of the system determine their side effects. (Click the picture below to enlarge.)

Parthenolide, in the above image, is an active ingredient found in feverfew.

Corticosteroids are effective in reducing inflammation in large part because of their effect on NF-kB. But steroids also result in many different and unrelated effects. Effects not associated with the NF-kB system account for the many serious side effects associated with steroid use.

Generally speaking, natural products are relatively weak, but have few side effects. Synthetic drugs are stronger, but have many side effects. Banjo is an attempt to enhance the efficacy of natural products without changing the generally favorable side effect profile associated with natural agents.