Posts tagged interleukin
Articles and news from the latest research reports.
Halting Immune Response Could Save Brain Cells After Stroke
A new study in animals shows that using a compound to block the body’s immune response greatly reduces disability after a stroke.
The study by scientists from the University of Wisconsin School of Medicine and Public Health also showed that particular immune cells – CD4+ T-cells produce a mediator, called interleukin (IL)-21 that can cause further damage in stroke tissue.
Moreover, normal mice, ordinarily killed or disabled by an ischemic stroke, were given a shot of a compound that blocks the action of IL-21. Brain scans and brain sections showed that the treated mice suffered little or no stroke damage.
“This is very exciting because we haven’t had a new drug for stroke in decades, and this suggests a target for such a drug,” says lead author Dr. Zsuzsanna Fabry, professor of pathology and laboratory medicine
Stroke is the fourth-leading killer in the world and an important cause of permanent disability. In an ischemic stroke, a clot blocks the flow of oxygen-rich blood to the brain. But Fabry explains that much of the damage to brain cells occurs after the clot is removed or dissolved by medicine. Blood rushes back into the brain tissue, bringing with it immune cells called T-cells, which flock to the source of an injury.
The study shows that after a stroke, the injured brain cells provoke the CD4+ T-cells to produce a substance, IL-21, that kills the neurons in the blood-deprived tissue of the brain. The study gave new insight how stroke induces neural injury.
Similar Findings in Humans
Fabry’s co-author Dr. Matyas Sandor, professor of pathology and laboratory medicine, says that the final part of the study looked at brain tissue from people who had died following ischemic strokes. It found that CD4+ T-cells and their protein, IL-21 are in high concentration in areas of the brain damaged by the stroke.
Sandor says the similarity suggests that the protein that blocks IL-21 could become a treatment for stroke, and would likely be administered at the same time as the current blood-clot dissolving drugs.
“We don’t have proof that it will work in humans,” he says, “but similar accumulation of IL-21 producing cells suggests that it might.”
The paper was published this week in the Journal of Experimental Medicine.
(Source: med.wisc.edu)
Alzheimer’s Disease in Mice Alleviated Promising Therapeutic Approach for Humans
Pathological changes typical of Alzheimer’s disease were significantly reduced in mice by blockade of an immune system transmitter. A research team from Charité - Universitätsmedizin Berlin and the University of Zurich has just published a new therapeutic approach in fighting Alzheimer’s disease in the current issue of Nature Medicine. This approach promises potential in prevention, as well as in cases where the disease has already set in.
The accumulation of particular abnormal proteins, including amyloid-ß (Aβ) among others, in patients’ brains plays a central role in this disease. Prof. Frank Heppner from the Department of Neuropathology at Charité and his colleague Prof. Burkhard Becher from the Institute for Experimental Immunology at the University of Zurich were able to show that turning off particular cytokines (immune system signal transmitters) reduced the Alzheimer’s typical amyloid-ß deposits in mice with the disease. As a result, the strongest effects were demonstrated after reducing amyloid-ß by approximately 65 percent, when the immune molecule p40 was affected, which is a component of the cytokines interleukin (IL)-12 and -23.
Inflammation and Cognition in Schizophrenia
There are a growing number of clues that immune and inflammatory mechanisms are important for the biology of schizophrenia. In a new study in Biological Psychiatry, Dr. Mar Fatjó-Vilas and colleagues explored the impact of the interleukin-1β gene (IL1β) on brain function alterations associated with schizophrenia.
Fatjó-Vilas said that “this study is a contribution to the relatively new field of ‘functional imaging genetics’ which appears to be potentially powerful for the study of schizophrenia, where genetic factors are of established importance and cognitive impairment – affecting particularly executive function and long-term memory – is increasingly recognized as a core feature of the disorder.”
To conduct this study, they recruited patients with schizophrenia and healthy volunteers, all of whom completed a working memory task while undergoing a functional magnetic resonance imaging scan in the laboratory. This allowed the researchers to determine which areas of the brain became activated during the task. Each participant was also genotyped to determine which allelic combination of the -511C/T polymorphism at the promoter region of the IL1β gene they carry: CC, TT, or CT.
Patients who were homozygous for the C allele (CC) showed reduced prefrontal cortex activation associated with working memory than patients who had at least one copy of the T allele. Among the healthy volunteers, frontal brain activation did not differ according to genotype.
“The analyzed genetic variant exerts an influence on prefrontal cortex function and this influence is different in healthy subjects and patients with schizophrenia,” summarized Fatjó-Vilas.
An important issue is that the -511C/T seems to have a role in regulating the levels of IL1B expression, in which case it would influence neuronal activity dependent on the protein availability. This means that the T allele has been reported to be more active than the C allele, suggesting that a tendency for greater expression of IL1β is associated with greater compromise of frontal cortical functions underlying cognition.
Interleukin-1β is released in the blood under stressful conditions and its release is one of the ways that stress promotes inflammation. IL-1β levels in the blood are altered, for example, in patients with depression and other neuropsychiatric disorders.
Apart from having a role in the immune system, interleukins are also involved in a variety of developmental and functioning processes of the central nervous system. Thus, this study provides further clues for identifying specific biological mechanisms of the disorder associated with both neurodevelopmental processes and immunological and stress response functions.
Dr. John Krystal, Editor of Biological Psychiatry, commented, “We are just beginning to explore the functional impact of inflammatory mechanisms in schizophrenia and the current findings increase our curiosity about these novel mechanisms.”
(Source: alphagalileo.org)