(Selected Tables and Figures referenced, but not present in this blog
can be found in their corresponding Science Version blogs)
We started our last blog (#14) on chronic inflammation (CI) by describing its differences with acute inflammation. They included the causes of CI; its types of overreactions triggered by the immune cells; its chemical or pharmacologic differences; and finally, its clinical presentation. We really covered only the first and second difference, namely the causes and the cellular immune overreactions of CI. So we have a lot more work to do. Let’s get through CI’s chemical, pharmacology and pharmacodynamics in this blog and then finish up with the clinical and immunotherapeutic considerations of CI in Blog #15.
The pharmacology of CI includes a vast array of chemicals, enzymes, hormones and other reactive proteins as part of the inflammatory cascade. All of their functions are controlled in large part by the brain and we’ll be discussing them more in Blog #17. Meanwhile, the chemical actions that drive the immune response, or the pharmacodynamic process, is another portion of the CI reactions. All sorts of chemical mediators or “immunomodulators” that are actively amplifying, supplementing or suppressing CI reactions are producing the therapeutic effects we’ll be discussing in the next blog. The active immune cells in the process are generating some very potent chemicals of their own like interleukins, cytokines and one in particular protein called tumor necrosis factor alpha or TNA-a responsible for a wide range of signals that lead to those unique CI reactions we mentioned previously, like necrosis, fibrinization, and apoptosis. An interesting feature of this TNA-a protein is its multiple functions as a proinflammatory chemical that can resist infection and it also plays a role in cancer treatments. As such, numerous drugs have been developed to inhibit TNA-a to control inflammation and conversely, drugs to stimulate it to treat infection and cancer. Confusing? Indeed, it’s a delicate balancing act when modulating these pharmacologic agents in immunotherapies. But this whole area of CI pharmacology and pharmacodynamics illustrates CI’s role in all disease processes.
Allow me to dive just a little deeper for a moment into the pharmacodynamics of CI for some more robust, albeit complex, but worthwhile information. Think back to those WBCs that were activated by APCs (remember antigen presenting cells from back in Blog #5?) and immune chemicals that escaped from the blood vessels to fight a disease process site(s). On activation, one of those WBCs, the neutrophil, is being strengthened by all those mediators to aggressively help destroy the antigen by a powerful process called phagocytosis. This neutrophil process adds significantly to cytokines, TNF-a, T- and B-lymphocytes and antibodies that are attempting to mediate inflammation along with those hypersensitivity overreactions (the Type 1 to 4 reactions from Blog #5). Meanwhile, adding to the inflammatory process are circulating blood platelets playing a role in the inflammatory process by adhering to the vessel walls forming thrombus; and other types of unique cells like mast cells giving off histamine and other inflammatory mediators producing the classic IgE allergic response (from Type I hypersensitivity). Quite a demonstration of biochemistry and, in fact, the basis for our in-depth immunotherapy upcoming discussion in Blog #21. What was the old DuPont saying? “Better living through chemistry.” Oops! I’m giving away my age?
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