Keith W. Kelley

Professor of Immunophysiology, Department of Animal Sciences, College of ACES; Department of Pathology, College of Medicine; Division of Nutritional Sciences and Neuroscience Program
Editor-in-Chief, Brain, Behavior, and Immunity
B.S., 1969, Illinois State University
M.S., 1973, University of Illinois
Ph.D., 1976, University of Illinois

Research Areas

The physiology of immunology

Together with Robert Dantzer, we have been involved for the past 30 years in defining reciprocal systems of communication between the immune and central nervous systems. We established early on that IL-1β and TNFα serve as communication molecules between the immune and central nervous systems. In contrast, anti-inflammatory cytokines in the brain, such as IL-10 and IGF-I, reduce behavioral symptoms of sickness following acute activation of the innate immune system. However, if systemic inflammation continues unabated, the tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO) is activated, which is well known to impair T cell proliferation. We have used both pharmacologic and genetic approaches to establish that infection with bacille Calmette-Guérin (BCG), an attenuated form of Mycobacterium bovis, induces persistent activation of IDO in the brain and is responsible for development of depressive-like behavior. In addition to standard quantitative assessments of sickness and depressive-like behaviors in pre-clinical murine models using a variety of floxed and inducible genes, the major laboratory techniques employed are tissue culture of primary and transformed cells, organotypic hippocampal slice cultures, immunohistochemistry, flow cytometry, Western blots, ELISAs, real-time RT-PCR and HPLC. The major health impact of our research is directed at behavioral changes that occur in costly human diseases ranging from cancer to AIDS.

Representative Publications

Willemen, H.L.D.M., N. Eijkelkamp, R. Dantzer, G.W. Dorn II, K.W. Kelley, C.J. Heijnen and A. Kavelaars. 2010. Microglial/macrophage GRK2 determines duration of peripheral IL-1β-induced hyperalgesia: contribution of spinal cord CX3CR1, p38 and IL-1 signaling. Pain (In Press).

Raison, C.L., M. Lawson, R. Dantzer, K.W. Kelley, B.J. Woolwine, G. Vogt, J. Spivey, K. Saito and A.H. Miller. 2010. CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFNα: Relationship to CNS immune responses and depression. Mol. Psychiatry. 15:393-403 PMCID: 2844942.

Wang, Y., M.A. Lawson, R. Dantzer and K.W. Kelley. 2010. LPS-induced indoleamine 2,3-dioxygenase is regulated in an interferon-γ-independent manner by a JNK signaling pathway in primary murine microglia Brain Behav. Immun. 24:201-209 PMCID: 2818058.

O'Connor, J.C., M.A. Lawson, C. André, E.M. Briley, S.S. Szegedi, J. Lestage, N. Castanon, M. Herkenham, R. Dantzer and K. W. Kelley. 2009. Induction of IDO by Bacille Calmette-Guérin is responsible for development of murine depressive-like behavior. J. Immunology 182:3202-3212 PMCID: 2664258.

O'Connor, J.C., C. André, Y. Wang, M.A. Lawson, S.S. Szegedi, J. Lestage, N. Castanon, K.W. Kelley and R. Dantzer. 2009. Interferon-γ and tumor necrosis factor-α mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to Bacillus Calmette-Guérin. J. Neuroscience 29:4200-4209. PMCID: 2835569.

O'Connor, J.C., M.A. Lawson, C. André, M. Moreau, J. Lestage, N. Castanon, K.W. Kelley and R. Dantzer. 2009. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol. Psychiatry 14:511-522 PMCID: 2683474.

Palin, K. R.M. Bluthé, R.H. McCusker, T. Levade, F. Moos, R. Dantzer and K.W. Kelley. 2009. The type 1 TNF receptor and its associated adapter protein, FAN, are required for TNFα-induced sickness behavior. Psychopharmacology 201:549-556 PMCID: 2711641.

Dantzer, R., J.C. O'Connor, G.G. Freund, R.W. Johnson and K.W. Kelley. 2008. From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neuroscience 9:46-56 PMID: 1807377.

Jang, S., K.W. Kelley and R.W. Johnson. 2008. Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proceedings of the National Academy of Sciences USA 105:7534-7539 PMCID: 2396685.

Huey, K.A., R.H. McCusker and K.W. Kelley. 2008. Exaggerated expression of skeletal muscle-derived interleukin-6, but not TNFα, in mice lacking intereukin-10. J. Neuroimmunology 199:56-62 PMCID: 2578822.

Dantzer, R. and K.W. Kelley. 2007. Twenty years of research on cytokine-induced sickness behavior. Brain, Behavior, and Immunity 21:153-160. doi:10.1016/j.bbi.2006.09.006.

Strle, K., S.R. Broussard, R.H. McCusker, W.H. Shen, J.M. LeCleir, R.W. Johnson, G.G. Freund, R. Dantzer and K.W. Kelley. 2006. C-jun N-terminal kinase mediates TNFα suppression of differentiation in myoblasts. Endocrinology 147:4363-4373. doi:10.1210/en.2005-1541.

Additional Information

Collaborative projects

Professor Robert Dantzer – Neuroimmune control of biobehavioral processes

Lab

Keith Kelley shares office and laboratory space with Professor Robert Dantzer in 227, 250 and 261 ERML, respectively.