Keith 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

Cross talk between cytokine and hormone receptors

Inflammation is now recognized to be responsible for major health problems of the aging population, contributing to costly diseases such as obesity, the metabolic syndrome, heart disease and insulin resistance in type-2 diabetes. Our laboratory is involved in defining reciprocal systems of communication between the immune system and brain. We have shown that IL-1β, TNFα and IL-6 serve as communication molecules between the immune and central nervous systems, and we are now trying to decipher the pathways by which that communication occurs. Recently, we discovered the existence of intracellular crosstalk between receptors for proinflammatory cytokines (TNFα, IL-1β) and hormones (IGF-I) in a variety of cells. These data show that the biological properties of a classical hormonal growth factor receptor, IGF-I, are directly regulated by proinflammatory cytokines from the immune system. Other major research projects are aimed at determining the actions of proinflammatory cytokine receptors that cause sickness and depression-like behavior as well as changes in cognition. In contrast, anti-inflammatory cytokines in the brain, such as IL-10 and IGF-I, reduce behavioral symptoms of sickness. Indeed, we and others have collected substantial evidence to show that inflammation status, as defined by the overexpression of proinflammatory cytokines, is not restricted to the periphery but is also found in the brain. Brain inflammation causes symptoms of sickness and depression, both of which are likely to be important contributors to comorbid behavioral and psychological disturbances that occur in the elderly. Aged mice are more susceptible to sickness- and depression-like behavior than adults. We are testing the hypothesis that peripheral inflammation causes greater neuroinflammation and activation of the tryptophan-degrading enzyme, indoleamine 2,3 dioxygenase (IDO), in aged than adult mice. This enzyme leads to the induction of depression-like behavioral alterations and may be exacerbated during aging.

Representative Publications

Dantzer R, O’Connor JC, Freund GG, Johnson RW, and Kelley KW. (2008) From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neurosci, 9, 46-56.  

Godbout JP, Moreau M, Lestage J, Chen J, Sparkman NL, O’Connor J, Castanon N, Kelley KW, Dantzer R, and Johnson RW. (2007) Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system, Neuropsychopharmacology,  Dec 12; [Epub ahead of print]

O'Connor JC, Lawson MA, Andre C, Moreau M, Lestage J, Castanon N, Kelley KW, and Dantzer R. (2008) Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiat, Jan 15; [Epub ahead of print].

Mingam R, Smedt VD, Amédée T, Bluthé RM, Kelley KW, Dantzer R, and Layé S. (2007)  In vitro and in vivo evidence for a role of the P2X(7) receptor in the release of IL-1beta in the murine brain, Brain Behav Immun, 22, 234-244.

Abraham JS. Jang JP, Godbout J, Chen, Kelley KW, Dantzer R, and Johnson RW. (2007) Aging sensitizes mice to behavioral deficits induced by central HIV-1 gp 120. Neurobiology of Aging (In Press)

Strle, K, McCusker RH, Tran L, King A, Johnson RW, Freund GG, Dantzer R, and Kelley KW. (2007) Novel activity of an anti-inflammatory cytokine: IL-10 prevents TNFα-induced resistance to IGF-I in myoblasts. J. Neuroimmunology 188:48-55.

Palin, K, Bluthé RM, McCusker RH, Moos F, Dantzer R, and Kelley KW. (2007) TNFα-induced sickness behavior in mice with functional 55 kD TNF receptors is blocked by central IGF I. J. Neuroimmunology 187:55-60.

Frenois, F, Moreau M, O’Connor JC, Lawson M, Micon C, Lestage J, Kelley KW, Dantzer R, and Castanon N. (2007) Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior. Psychoneuroendocrinology 32:516-531.

Kelley KW, Weigent DA, and Kooijman R. (2007) Protein hormones and immunity. Brain, Behavior, and Immunity 21:384-392.

Dantzer R, and Kelley KW. (2007) Twenty years of research on cytokine-induced sickness behavior. Brain, Behavior, and Immunity 21:153-60.

Strle K, Broussard SR, McCusker RH, Shen WH, LeCleir JM, Johnson RW, Freund GG, Dantzer R, and Kelley KW. (2006) C-jun N-terminal kinase mediates tumor necrosis factor-α suppression of differentiation in myoblasts. Endocrinology 147:4363-73.

McCusker, RH., McCrea K, Zunich S, Dantzer R, Broussard SR, Johnson RW, and Kelley KW. (2006) Insulin-like growth factor-I enhances the biological activity of brain-derived neurotrophic factor on cerebrocortical neurons. J. Neuroimmunology 179:186-190.

Kelley, KW. (2004) Norman Cousins Lecture: From hormones to immunity: The physiology of immunology. Brain, Behavior, and Immunity 18:95-113.

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.