Infectious inflammation of the CNS involves activation of mitogen-activated protein kinase and AKT proteins in CSF in humans

Abstract

The mitogen-activated protein kinases (MAPKs) and the AKT are interacting proteins that serve as transmitters of numerous extracellular signals to their intracellular targets, thereby regulating many cellular processes, such as proliferation, differentiation, development or stress responses. Whereas a large amount of information about the MAPKs/AKT participation in biological processes is available, less is known about their role in human diseases. We postulated that the MAPKs/AKT could be involved in inflammatory processes of the central nervous system (CNS) in humans and we investigated the CSF of 12 patients with viral infection of the CNS for the presence of the distinct components of these cascades. The cerebrospinal fluid (CSF) of 18 individuals who underwent a lumbar puncture for diagnostic purposes served as controls. Six patients with inflammatory disease of the CNS revealed the presence of activated ERK. In five patients p38MAPK was detected, in three in its activated form. The activity of AKT could be demonstrated in four patients. JNK was not found. None of the control patients showed the presence of MAPK enzymes. The mean CSF cellularity was higher in MAPK-positive than in MAPKnegative patients. There was no difference in mean age or gender between the patients and controls, or between the MAPK- and AKT-positive or -negative patients. Our work demonstrates that the MAPK and AKT cascades might participate in inflammatory processes of the CNS. As selective inhibitors of the MAPKs are available, their application in the future might reduce an inappropriate inflammatory response and thus limit brain damage in severe cases of meningoencephalitis.