Body's protein does malaria's dirty work.

Body's protein does malaria's dirty work

The often-deadly anemia brought on by severe malaria has long puzzled researchers because its victims' red blood cells perish much faster than the malaria parasite alone should destroy them. Now two scientists have implicated a villain tha normally plays the hero -- an immune-system protein called tumor necrosis factor, or TNF.

The body makes TNF to aid in healing and to fight infections or tumors, but in excess this potentially toxic substance can devour red blood cells. Infection by Plasmodium berghei, the deadliest and most prevalent strain of malaria parasite, can spur production of excess TNF.

Scientists first suggested a connection between malaria and TNF in 1981 after observing that TNF given to cancer patients and laboratory animals brought on the same symptoms as malaria. In the May INFECTION AND IMMUNITY, Kathleen L. Miller, Paul H. Silverman and colleagues of the Lawrence Berkeley Laboratory in Berkeley, Calif., report the first evidence that TNF exacerbates the anemia that kills many malaria patients.

Miller and Silverman mimicked malarial anemia by injecting TNF into healthy mice. They noted that the TNF destroyed the precursors to red blood cells. In another experiment, the team partially reversed anemia in malaria-infected mice by giving them antibodies to TNF, which restored many of the depleted red blood cells. The antibodies worked by binding up the infection-induced TNF.

Miller thinks TNF antibodies could someday alleviate malarial anemia in people, but she cautions that blocking a normally useful protein might cause unforeseen harm. On the other hand, the benefits of a TNF-antibody treatment might outweigh its potential risks. Miller notes, for instance, that malaria victims in Africa face potentially AIDS-tainted blood transfusions. She hopes further research will lead to a safe treatment based on carefully controlled doses of TNF antibodies to neutralize only the pathologically excessive TNF.

Scientists discovered TNF's tumor-fighting properties at the turn of the century after observing that cancer patients often improved when infected with bacteria. They later found that bacterial toxins stimulated the patients' bodies to produce more TNF, which in turn cut off the blood supply to their tumors. But when massive cancers or parasite infestations spur the body to produce too much, TNF can bring debilitation and death. Researchers once thought a separate substance, called cachectin, caused the "wasting away" so often seen in severe cancer cases. In 1985, they discovered that the "good" TNF and the "bad" cachectin are one and the same.