Answer by Jim Seidman:

This is a fascinating and complex question. There’s a phenomenon formally known as “Sickness behavior“, which includes lethargy, depression, anxiety, loss of appetite, sleepiness, increasing sensitivity to pain, reduction in grooming, and failure to concentrate. Anyone who has had a serious infectious disease has experienced at least some aspects of sickness behavior.

The current medical understanding is that sickness behavior is largely driven by inflammation’s effect on the brain. There are academic papers that seek to explain this process in detail, such as From inflammation to sickness and depression: when the immune system subjugates the brain. The process generally involves pro-inflammatory cytokines, which are proteins secreted by immune system cells that drive the inflammatory process.

The review article Cytokines and the Brain: Implications for Clinical Psychiatry points out the pro-inflammatory cytokine IL-1 is the best researched. IL-1 has four main mechanisms of effects of cytokines on the brain:

  1. Immunologic effects: IL-1 can cause cascades of production of other cytokines from cells in the brain, and trigger proliferation of blood vessels and glial cells.
  2. Neurochemical effects: IL-1 can trigger levels of neurotransmitters and their metabolites.
  3. Neuroendocrine effects: IL-1 can increase the activity of the hypothalamic, pituitary, and adrenal glands, and affect secretion of other hormones as well.
  4. Behavioral effects: this primarily refers to the sickness behavior I mentioned earlier. But in chronic cases, it can extend to driving psychiatric disorders including depression, schizophrenia, and Alzheimer’s disease.

There are, similarly, anti-inflammatory cytokines that modulate the inflammatory process. Anti-inflammatory therapies may either cause the production of anti-inflammatory cytokines, or inhibit the work of pro-inflammatory cytokines. For example, there are several drugs such as Remicade, Tysabri, and Humira that work by directly binding to specific cytokines. Other types of anti-inflammatory drugs may or may not affect the levels of cytokines depending on where they interrupt the process: e.g., drugs such as aspirin and ibuprofen inhibit prostaglandin production, which is caused by (and not generally a cause of) cytokine production. In most cases, anti-inflammatory drugs are going to leave a lot of various cytokines floating around. It’s therefore very hard to predict the extent to which such a drug will stop the impact of the inflammatory process on the brain.

How does inflammation and anti-inflammatories affect the brain’s function?