- Calor heat
- Dolor pain
- Rubor redness
- Tumor swelling
What if, some medical researchers asked, we could damp down the immune response. That would alleviate many of the distressing symptoms of auto-immune diseases and might even promote a bit of healing in the damaged tissue. One of the positive outcomes of 30 years of molecular biological research is that we now have model incorporating some of the key players in the inflammatory response: both what molecules are involved and what cells play a part. As with the nervous system, we reckon that the cellular response is controlled by external molecules = "ligands" which dock and bind with receptors embedded in the cell membrane. "Molecules which are produced by one cell type and act on another cell not in immediate proximity" is a definition of a hormone. But in the context of immunology and inflammation such molecules tend to be called cytokines. Each cytokine will have a particular look&feel and function and will only be effective if it makes contact with a specific receptor. Both cytokines and their receptors are proteins of which we have an inventory of about 100,000 different forms, some quite closely related to each other. Clearly there are two ways to turn inflammation down a notch or two:
- destroy, disable or interfere with the production of one of the cytokines
- put a spanner in the cytokine receptor to prevent docking
One way of nobbling a cytokine is to develop a 'biologic' an antibody against that molecule. I've written before about the absurd unmemorable hard-to-say names for drugs. But there are some clues: if it ends in -mab it is a monoclonal antibody developed by injecting the . . . heck I'm not going to explain this because it's w-a-a-a-a-y outside my competence so I'll hand you off to John Nguyen at Massachusetts College of Pharmacy and Health Sciences - what's a MAb and how are they made.
More etymological clues:
- omab (original and not the best) = murine monoclonal antibody
- ximab = chimeric (part human part mouse) monoclonal antibodies like infliximab [prev]
- zumab = humanized (less mouse more human than ximabs)
- mumab = fully human monoclonal antibodies are made in human cell lines skipping the mouse protocol. Try saying adalimumab with clarity and authority when explaining its potential to a worried patient.
- Another John Nguyen gallop through a bunch of specific MAbs, their names pronounced and the uses described
The trouble is that although the MAb is extremely specific - it will take down TNF-α only - TNF-α is a key work-horse in maintaining homeostasis all around the body. By controlling the level of this cytokine to mitigate the debilitating effects of RA or IBD, the patient no longer has enough of the stuff to do its says-on-the-tin tumour necrosis job and lymphomas are a common side effect under long-term use of infliximab. This robbing Peter to pay Paul is a problem in many aspects of modern medicine and the good doctors spend a lot of time and money juggling the competing forces to get a drug and a dose that is a Goldiloxian just right. Cue not strictly relevant fragment of verse:
I balanced all, brought all to mind,
The years to come seemed waste of breath,
A waste of breath the years behind
In balance with this life, this death.
WB Yeats An Irish Airman foresees his death
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