Peripheral protein immunization induces rapid activation of the CNS, as measured by c-Fos expression.

To investigate immune-to-brain communication, we challenged rats intraperitoneally with a protein antigen (keyhole limpet hemocyanin, KLH), and measured c-Fos expression in different brain structures. We found a rapid c-Fos expression 120 min after immunization in brain stem and forebrain structures, using a dose of KLH not inducing fever or malaise. Using proper controls, we found that this central response is related to the immunogenicity of the antigen and the magnitude of the immune response. Our results suggest that different interconnected brain cell groups respond rapidly to an immune challenge in the periphery, constituting an afferent pathway of neuroimmune communication.