Collateral Damage  pg. 3

The messages transmitted between cells by cytokines are an essential part of the inflammatory response. Represented here as signal beams, cytokines produced by the epithelium (top right) can “recruit” neutrophils (circulating white blood cells, right) that can “rev up” inflammation. Meanwhile, a macrophage (bottom left) signals the blood vessel and fibroblasts (structural cells, top left) to play their various roles in fighting infection and repairing damaged tissue.
Illustration by Marie Guibert for Jean-Marc Cavaillon, Ph.D., Institut Pasteur.
The finding led to the development and the marketing of the blockbuster arthritis drugs Celebrex and Vioxx, which specifically inhibit the COX-2 enzyme without affecting the activity of COX-1. Thus, they were designed to relieve pain and inflammation without causing stomach upset and gastrointestinal bleeding, a problem with aspirin and other non-steroidal, anti-inflammatory drugs (NSAIDs) that block both enzymes.

The third arm of inflammatory mediators includes the cytokines, a large family of messenger proteins that—among other things—are involved in reproduction, the development of the embryo, maturation of blood cells and the immune response.

Cytokine production also is an essential part of the inflammatory response to infection or injury. Produced by a variety of cells in response to injury or infection, they communicate messages that help coordinate the processes of healing and fighting pathogenic invaders.

Cytokines involved in the inflammatory response include the interferon and interleukin families and tumor necrosis factor-alpha (TNF-alpha). Interferons and interleukins play a variety of roles; some of them “fuel the fire” of inflammation, while others dampen it.

Various treatments are being developed to either block pro-inflammatory members of the interleukin family or enhance the anti-inflammatory activities of others.

TNF-alpha, named for its ability to kill tumor cells, is thought to be at the center of inflammatory signaling. It can help recruit white blood cells to the site of inflammation, thereby boosting production of perhaps dozens of other cytokines.

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