INCREASED EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA RECEPTORS IN THE BRAINS OF PATIENTS WITH AIDS

Tumor necrosis factor (TNF)-alpha has been shown to be increased in br ain tissue of AIDS patients and may function as a mediator of cerebral damage. We initiated a study to determine the cellular localization a nd degree of protein and mRNA expression of the two specific TNF-alpha receptors (TNF-Rs), p55 and p75, in brain tissues from AIDS patients. Cerebral white matter obtained at autopsy from 13 AIDS patients, 10 u nhealthy controls, and 4 healthy controls was evaluated. Double-label immunohistochemistry revealed prominent up-regulation of p55 and p75 T NF-Rs on activated macrophages and microglial cells in all AIDS patien ts; no increased staining was found on astrocytes. Staining was most p rominent in patients with opportunistic infection of the brain and in microglial nodules of patients with HIV encephalitis. Brain tissues al so showed increased expression of interleukin (IL)-1 beta, IL-6, and T NF-alpha, cytokines known to up-regulate the TNF-Rs. Increased stainin g for TNF-Rs was also found in patients with multiple sclerosis, chron ic cerebral edema, and radiation necrosis but not in an asymptomatic H IV-positive patient without AIDS, Reverse transcriptase polymerase cha in reaction performed on adjacent sections from five AIDS patients rev ealed up-regulation from normal for p55 in all patients and for p75 in three patients. The up-regulation of both TNF-Rs in AIDS suggests tha t macrophages and microglial cells may be important in amplifying the TNF-alpha response.