What’s the Opposite of Inflammation?

I want to commemorate the writing of my 100th article on Blogspot by discussing a new insight into inflammation.

I have been searching the last several years for an anti-inflammatory system to balance inflammation. Now I realize that there is no opposite to inflammation. There is only completion of inflammation to return to the original state. Inflammation is a process that includes resolution or recovery from the defensive, destructive state of immunological activity.

Inflammation is the martialling of resources for battle by offloading lymphocytes from the blood stream, engaging the enemy by triggering the release of toxic secretory vesicles from leukocytes, and cleaning up the carnage by macrophages engulfing cellular fragments. Each step in the inflammatory process induces the next step until there is a return to the origin. Inflammation is not balanced by anti-inflammatory processes.

Inflammation is triggered by molecules characteristic of viruses, bacteria or fungi binding to membrane receptors (TLRs). The result is activation of the inflammatory transcription factor, NFkB (illustrated holding DNA), that turns on the expression of dozens of genes that code for cytokines (IL-1, IL-6, TNF) and enzymes (COX-2) that produce signal compounds. Among the signal compounds are the inflammatory eicosanoids (PGE2) produced from the omega-6 fatty acid arachidonic acid (ARA).

The complex signaling pathways that lead to PGE2 synthesis subsequently initiate transcription of genes that code for the enzymes that make lipoxins (resolvins and protectins) from eicosapentanaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are the two omega-3 fatty acid components of fish oil and a shortage of these dietary components blocks the next step, resolution of inflammation.

The lipoxins reduce the permeability of blood vessels, stop the offloading of lymphocytes, reduce responsiveness to inflammatory cytokines, recruit phagocytic macrophages to clean up debris and orchestrate a return to quiescence of the inflammatory system. Without adequate lipoxins, inflammation continues.

An interesting footnote to this discussion is the impact of aspirin on inflammation. Aspirin binds to the enzyme (COX-2) that converts ARA to inflammatory prostaglandins and leukotrienes. Acetylation of COX-2 by aspirin stops inflammatory eicosanoid synthesis and shifts the synthesis to anti-inflammatory lipoxins. Even ARA is used to make anti-inflammatory lipoxins in the presence of aspirin. This shift to anti-inflammatory signaling may occur naturally in the small intestines in response to aspirin-like compounds in vegetables. This would be a transitory response similar to taking aspirin with a meal. More constant use of aspirin would disrupt the normal and necessary actions of the inflammatory signaling to maintain the integrity of the gut.

Excess of dietary omega-6 oils and deficiency in omega-3 fatty acids corrupts inflammatory signaling by eliminating recovery and produces chronic inflammation. Another name for chronic inflammation is obesity/metabolic syndrome. Chronic inflammation is the foundation for the degenerative, autoimmune and cancer diseases that are so prevalent today.

Fortunately a shift to an anti-inflammatory diet and lifestyle provides a simple solution to chronic inflammation.

[Note added: Perhaps the opposite of anti-inflammatory is immunosuppressed, as in high use of omega-3 oils can increase the risk of tuberculosis of influenza.]