A study of 2,480 AIDS patients has found that they have 2.4 times the risk of contracting non-Hodgkin's lymphoma (NHL) if they carry a certain polymorphism. Charles S. Rabkin, HIV-cancer coordinator at the National Cancer Institute, presented this preliminary finding at last month's meeting of the American Association for Cancer Research in New Orleans. The polymorphism, a cytosine-for-guanine substitution in the interleukin-6 gene's promoter region, results in decreased plasma levels of IL-6. Rabkin initially predicted that lower levels would reduce NHL risk because IL-6 stimulates B cells and thus might promote the development of lymphoma. To account for his contrary finding, he speculates that inadequate IL-6 might result in poorer control of HIV infection, which, in turn, leads to more insults to lymphocytes and finally to NHL. In the study, 60 percent of Caucasians had at least one copy of the polymorphism (the difference in NHL risk between homozygotes and heterozygotes was statistically insignificant). But only 16 percent of African-Americans had a copy, which might contribute to their lower risk of contracting AIDS-related lymphoma. The study also linked the polymorphism to higher risks of dementia, cytomegalovirus disease, and herpes simplex virus infection, and a lower risk of tuberculosis. "If this solidifies as a finding, you would want to try to make sure that people had adequate interleukin-6 activity," says Rabkin, adding, however, that IL-6 is "not a practical drug to administer now." Next on his agenda is determining how the polymorphism affects non-HIV-infected people.
New Role for Glia
Research from the last several years has shown that the brain's glial cells do much more than deliver nutrients and clear waste as had been previously thought. Inspired by studies suggesting that glial cells play a part in higher level brain functions once assigned only to neurons, a research group from the University of Colorado Health Sciences Center (UCHSC) decided to investigate whether astrocytes, a type of glial cell, express nicotinic acetylcholine receptors, which have been linked to brain-signal transmission, memory formation, smoking addiction, and diseases such as schizophrenia. In a recent study, they report that cultures express nicotinic receptors in rat primary cultures in vitro (G. Sharma, S. Vijayaraghavan, "Nicotinic cholinergic signaling in hippocampal astrocytes involves calcium-induced calcium release from intracellular stores," Proceedings of the National Academy of Sciences, 98:4148-53, March 27, 2001). According to senior author Sukumar Vijayaraghavan, an assistant professor of physiology and biophysics at UCHSC, investigators had previously suspected that astrocytes expressed nicotinic receptors. "What wasn't known," he says, "was what kind of receptors and what the signaling mechanism was." Although the astrocytes were found to express only low levels of nicotinic receptors, they efficiently raised intracellular calcium levels, suggesting a different mechanism of calcium signaling than observed in neurons. "This sort of adds an additional dimension to nicotinic signaling," comments Vijayaraghavan. He is quick to point out that before concluding anything about what the findings might mean for the biology of addiction, investigators must study nicotinic receptor expression in vivo.
