Chinese Researchers Illuminate Mechanism Involved in Thalidomide’s Prevention of PF

Thalidomide — a controversial drug that caused thousands of birth defects throughout Europe in the late 1950s and was more recently approved to treat multiple myeloma — may also in fact prevent pulmonary fibrosis (PF), Chinese researchers say.

Their study, “Anti-inflammation and Antioxidant Effects of Thalidomide on Pulmonary Fibrosis in Mice and Human Lung Fibroblasts,” appeared in the journal Inflammation.

PF is characterized by oxidative stress — an imbalance of chemicals known as free radicals — and an accumulation of inflammatory cells in the lungs that secrete various factors which cause pulmonary fibrosis. Oxidative stress refers to an imbalance of chemicals called free radicals in our body that can cause harmful effects.

Thalidomide, which was originally marketed as a sedative or hypnotic agent, is effective against inflammation and helps balance the immune system. It has also been useful in treating PF.

Researchers at China’s General Hospital of Tianjin Medical University wanted to see what effect thalidomide had on mouse models of PF and on human lung inflammatory cells. To do so, they induced the disease into the mice using bleomycin, a drug known to cause lung fibrosis. Then they injected the mice with varying doses of thalidomide every day for eight days.

The researchers determined thalidomide’s effects by looking at lung tissue under a microscope, as well as by measuring inflammation and oxidative stress. Results showed that thalidomide did, in fact, decrease PF. Furthermore, mice treated with the drug had a significantly lower lung wet/dry ratio, indicating less injury of the lungs.  (histopathology), the lung wet/dry ratio, levels of inflammatory markers and levels of markers indicative of oxidative stress.

In addition, mice treated with thalidomide had significantly lower levels of markers of inflammation such as IL-6, IL-8, TNF-α and TGF-β — a result also found in human lung cells treated with thalidomide.

First marketed in West Germany in 1957, thalidomide was pulled from the market in the early 1960s after an estimated 10,000 babies in 46 countries were born with severe birth defects, including deformed arms, legs, eyes, hearts and urinary tracts; only half of those children survived. Today, the drug is used mainly to treat leprosy and certain cancers such as multiple myeloma; the U.S. Food and Drug Administration approved its use as a multiple myeloma therapy in 2006.