Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
The evidence seemed convincing beyond a reasonable doubt that a protein called interleukin-12 was guilty big-time of having a hand in causing autoimmune disorders. IL-12 is a cytokine derived from the immune system's antibody-creating B lymphocytes and cell debris-scavenging macrophages.
Now, a neighboring molecule, interleukin-23, has been fingered as the true perpetrator of the autoimmune rap. That leaves IL-12 the victim of a case of mistaken identity.
The true bill appears in Nature dated Feb. 13, 2003, under the title: "Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain." Its authors are immunologists at DNAX Research Inc. in Palo Alto, Calif.
They charge that IL-12 has been wrongly accused - at least in the case of a cerebral autoimmune disease in mice - and that the real culprit is its close molecular relative, IL-23. Interleukin-12 is customarily seen as being a link between the immune system's innate and adaptive strategies. Frontline innate immunity employs mainly macrophages and dendritic cells, which respond to generic features of intruders, and react accordingly. Both gobble up alien microorganisms, and also release IL-12, which is important as defense against pathogens holed up inside cells of the body.
The prosecution's brief citing interleukin-12's ability to stimulate the backup adaptive immunity led to the accusation that IL-12 actively contributes to several autoimmune ills, including rheumatoid arthritis and inflammatory bowel disease. Another count in the indictment showed IL-12 found in people with multiple sclerosis, a disease of the central nervous system. But the accused protein now seems to have an alibi. Unlike other cytokines, which are produced by a single gene, IL-12 is composed of two proteins, p35 and p40, each encoded by a separate gene. The p35 subunit is multiplied nonstop by macrophages and dendritic cells, whereas p40 is generated only when these cells encounter pathogens.
The problem is that interleukin-12 is just one member of a small family of dimeric (two-molecule) cytokines that regulate gamma interferon production. And to confuse the jury, p40 is a component of both interleukin-12 and the newly discovered interleukin-23. The DNAX co-authors cloned mice that lacked IL-23 but not IL-12. They then compared the development of a classical multiple sclerosis (MS) model, namely EAE - experimental autoimmune encephalomyelitis. Administering IL-23 to these mice was enough to provoke the MS-mimicking EAE disease. As for the future role of IL-12, the jury is still out.
"Certainly there is far more complexity here than initially envisioned," observes a News & Views commentary accompanying the Nature article, "but this gives ample opportunity for [therapeutic] intervention."
An IL-1 Receptor Drug, Which Treats Rheumatoid Arthritis, Also Stops Sundry Solid Tumors Short
Can cancer and arthritis treatments be one and the same? Scientists at the Ben-Gurion University in Beer-Sheva, Israel, vote in the affirmative on this question. Their paper in the current Proceedings of the National Academy of Sciences (PNAS), released Feb. 18, 2003, carries the headline: "IL-1 is required for tumor invasiveness and angiogenesis."
The Israeli team found, paradoxically, that a natural protein, which contributes to joint destruction in arthritis, also may encourage cancerous tumor growth by angiogenesis. This process nourishes nascent tumors with a spreading network of blood vessels freighted with oxygen and nutrients. Researchers point out that interleukin-1, which has various inflammatory, immune and growth-promoting properties, is a protein previously implicated in arthritis.
The Israeli team recruited knockout mice missing the IL-1 gene. They injected both those KO animals and a control group with skin, breast or prostate cancer cells. The controls developed tumors and died within 20 days, whereas the KO mice stayed tumor-free for much longer, and some never developed cancer at all. The co-authors were able to prompt tumor angiogenesis in their KO mice by injecting them with IL-1. Conversely, angiogenesis was arrested in the control animals by treating them with IL-1Ra, a chemical that blocks IL-1 receptors, and is currently used to treat rheumatoid arthritis.
Not Handwriting On The Wall But In Chromosome Telomeres Predicts Likelihood Of Longevity
Foreseeing when you're most likely to die of old age is reliably recorded in your life blood. A paper in The Lancet dated Feb. 1, 2003, tells the story. It's titled: "Association between telomere length in blood and mortality in people aged 60 years or older." The authors are geneticists at the University of Utah in Salt Lake City.
They highlight how measuring the ends of chromosomes in older people could indicate their risks of dying from ills associated with superannuation. Telomeres, the tip-ends of chromosomes, shorten with age, and this shrinkage may aggravate the increased chances of disease and death. The authors cite the genetic disorder dyskeratosis congenita, in which telomere shortening speeds up and patients experience premature onset of many age-related diseases - plus early death.
The article's authors studied 143 individuals older than 60. People with shorter telomeres had higher mortality rates, linked with a threefold risk of death from heart disease and more than an eightfold risk of death from infectious diseases.
"This is the first research study," the Lancet article's senior author commented, "showing that telomere length is predictive of survival in humans. If this is correct," he added, "then it may be possible to extend the duration of healthy adult life using medical interventions that maintain telomere length."
Taking Aim At 466 Transit Peptides' In Malarial Parasite Suggests Correct Targeting' Approach
Plant cell biologists have identified 466 proteins in the malaria parasite Plasmodium falciparum that may be fruitful targets for antimalarial drugs. These "transit peptides" are responsible for regular deliveries of proteins to parasite organelles, called plastids, or apicoplasts. Because plastids do not occur in humans, putting an embargo on these deliveries might shut down the parasites and their plastid organelles, without harming the human host.
The authors report their findings in Science dated Jan. 31, 2003, in a paper titled: "Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum."