Apr. 23, 1997 Cocaine may weaken the body's natural defenses by dramatically altering the numbers and genetic machinery of an important type of immune cell from the thymus gland, according to researchers at the University of Illinois at Chicago and at the Veterans Administration West Side Medical Center. Their findings were published in the February 1997 issue of the Proceedings of the Society for Experimental Biology and Medicine.
"In mice and cell cultures, we found that cocaine directly affects many aspects of thymocyte functions," says David Ou, clinical associate professor of pathology at UIC and chief of immunology and virology at the VA West Side Medical Center. "Since the thymus is the essential organ for T-cell maturation and normal immune function, the effects of cocaine may partly explain abnormal immune responses, leading to increased disease or tumor growth."
The thymus gland plays a crucial role in the body's defense against viruses and other infections by producing T-lymphocytes that can attack foreign cells or tumors as well as regulate the production of antibodies. While previous studies have found increased rates of bacterial and viral infections in cocaine abusers, there have been few studies on the effects of cocaine on the thymus.
In the study conducted at the VA West Side Medical Center, Ou and his research colleagues injected mice daily for five days with either saline or varied doses of cocaine and analyzed different subpopulations of T-lymphocytes four hours after the last injection. They found significant decreases in the numbers of one key group of these immune cells. Their analysis revealed that as the dosage of cocaine increased, so did the rate of these cells undergoing programmed cell death with apoptosis.
In addition, the researchers found that the injections of cocaine resulted in much higher DNA material within the surviving thymocytes but without increasing genetic activity.
"These results suggest that cocaine may affect the process of T-cell maturation leading to an alteration of the normal immune function," says Ou. "We hypothesize that cocaine harms the immune system by altering the regulatory functions of key immune cells, resulting in increased susceptibility to cancer and infection."
"The thymocyte population is normally characterized by a rapid and extensive increase, followed by a tremendous decrease," explains Ou. "This unusual population fluctuation implies a high level of genetic activity that is vulnerable to outside influence."
The researchers also found similar results when they cultured normal thymocytes (from mice) with cocaine, with the cell survival rate declining as cocaine concentrations increased. Ou says the comparable findings suggest that cell-culture studies may be useful in studying cocaine effects on thymocyte biology.
"These findings certainly open new avenues for research into the effects of cocaine on the immune system," says Ou. "We now believe that cocaine can reduce thymocytes through direct contact with those cells, before it is metabolized in the body. Also, our finding that cocaine results in increased DNA content in thymocytes suggests that cocaine may have effects at the genetic level.
"Although our research on cocaine was limited to mice, we are concerned that abusers of this drug are making themselves more susceptible to disease and infection," Ou adds.
According to the National Institute on Drug Abuse, in 1994, about 22 million Americans age 12 and older had used cocaine at least once in their lifetimes; in 1995, about five percent of 10th-graders and six percent of 12th-graders had tried cocaine at least once. Ou says the implication of these findings for young people is serious because the thymus is more active in the young and is more vulnerable to the effects of cocaine.
The other researchers who collaborated in this study were: Yu-Bin Wu of the VA West Side Medical Center, Guo-Gang Gu of UIC's department of pathology, and Ken Anderson of Rush Medical College.
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