Hematopoietic Growth Factors: Part 2, Wound-Healing Factors

by Food and Drug Administration (FDA)

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Gerrard compares research on neurotrophic factors today with interferon research 10 years ago: "We don't know the precise effects of these neurotrophic factors, but we do know from laboratory study that they affect neurons — maybe preventing their death or promoting their biological activity. So we try them in diseases where we think this is important, such as Alzheimer's or ALS."

But, Gerrard explains, scientists don't understand the exact pathology of these diseases, either, so use of neurotrophic factors, again, takes a sort of shotgun approach.

"Since these are tragic diseases with not terribly good therapies," she says, "the idea is to try something that — even though we don't know exactly how it works — may show promise." But like Price, Gerrard counsels caution in clinical trials. John DiGiovanna, M.D., a dermatologist with the National Cancer Institute in Bethesda, Md., sees limited success so far in the use of interferons for various skin conditions.

"The anti-proliferative and cell-differentiating effects of interferon might be useful in destroying some types of skin tumors, for example, replacing the need for surgery," he says, "but the question of how well it actually does work is still somewhat controversial."

Even for approved uses, cytokine therapies — like many others — are not free of drawbacks. For example, he says, "Injections of alfa interferon three times a week for three weeks to treat genital warts can be expensive, awkward, painful, and the treatment doesn't have a very high cure rate." Nevertheless, DiGiovanna says, many conditions lack very effective treatments, and "it's always useful to have another avenue to try when others can't be used any more or don't work any more."

Wound-Healing Factors

On the other hand, Anita Roberts, Ph.D., optimistically envisions a host of future applications for another class of cytokines — wound-healing factors — that help orchestrate healing. Researchers are studying how these factors, given in larger quantities than those produced naturally, might speed the healing process.

Roberts, a cell biologist with the National Cancer Institute, is particularly interested in transforming growth factor beta (TGF- beta). Whenever wounding occurs, TGF-beta and another cytokine, platelet-derived growth factor (PDGF), are released. They attract to the site of the injury various cells needed to combat infection, cause clotting, and close the wound.

The mending abilities of TGF-beta are being studied in venous stasis ulcers (ulcers that develop in the leg because of insufficient blood flow), and to speed healing from eye surgery to repair macular holes. (The macula is the central part of the retina.) In topical form, the substance is applied directly to the wound.

"I think, even more important than these applications is the potential use of TGF-beta in normal wound healing," Roberts says, pointing to a study in rats, reported in the December 1993 Journal of Clinical Investigation, whose normal healing was suppressed by steroids.

In that study, a single intravenous injection of TGF-beta significantly improved healing in rats whether it was given at the time of wounding, four hours after wounding, or even 24 hours before wounding. Roberts suggests the cytokine might enhance healing in patients with a known impaired healing capacity, such as those undergoing high-dose radiation therapy or chemotherapy, or in elderly adults with impaired healing. She proposes it may also prove useful given before surgery in elective procedures to speed postoperative healing.

PDGF is being studied in humans for possible use in accelerating healing in chronic wounds, specifically diabetic foot ulcers, which are fairly well managed. If it proves effective for this type of sore, researchers may then try it in more serious wounds. Its effectiveness is also being tested in periodontal (gum) disease, where it is applied during surgery to help speed healing.

Is More Better?

Cytokines may be a case of "if a little is good, more must be better" — within reason, of course. These multipurpose proteins produced naturally by the body in tiny quantities may, in larger amounts, prove key to development of myriad new or improved medical treatments.

Cytokine research is still in its toddler-hood. Many more of these "messengers" besides the ones mentioned here are now being examined, and many more doubtless await scientists' future identification and scrutiny.

About the Author

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.