Rodney W. Johnson

Bio: Rodney W. Johnson is an academic researcher from University of Illinois at Urbana–Champaign. The author has contributed to research in topics: Proinflammatory cytokine & Sickness behavior. The author has an hindex of 63, co-authored 196 publications receiving 18156 citations. Previous affiliations of Rodney W. Johnson include Iowa State University & University of Illinois at Chicago.

From inflammation to sickness and depression: when the immune system subjugates the brain

Abstract: In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system

Abstract: Acute cognitive impairment (i.e., delirium) is common in elderly emergency department patients and frequently results from infections that are unrelated to the central nervous system. Since activation of the peripheral innate immune system induces brain microglia to produce inflammatory cytokines that are responsible for behavioral deficits, we investigated if aging exacerbated neuroinflammation and sickness behavior after peripheral injection of lipopolysaccharide (LPS). Microarray analysis revealed a transcriptional profile indicating the presence of primed or activated microglia and increased inflammation in the aged brain. Furthermore, aged mice had a unique gene expression profile in the brain after an intraperitoneal injection of LPS, and the LPS-induced elevation in the brain inflammatory cytokines and oxidative stress was both exaggerated and prolonged compared with adults. Aged mice were anorectic longer and lost more weight than adults after peripheral LPS administration. Moreover, reductions in both locomotor and social behavior remained 24 h later in aged mice, when adults had fully recovered, and the exaggerated neuroinflammatory response in aged mice was not reliably paralleled by increased circulating cytokines in the periphery. Taken together, these data establish that activation of the peripheral innate immune system leads to exacerbated neuroinflammation in the aged as compared with adult mice. This dysregulated link between the peripheral and central innate immune system is likely to be involved in the severe behavioral deficits that frequently occur in older adults with systemic infections.

Cytokine-induced sickness behavior

Abstract: The behavioral repertoire of humans and animals changes dramatically following infection. Sick individuals have little motivation to eat, are listless, complain of fatigue and malaise, loose interest in social activities and have significant changes in sleep patterns. They display an inability to experience pleasure, have exaggerated responses to pain and fail to concentrate. Proinflammatory cytokines acting in the brain cause sickness behaviors. These nearly universal behavioral changes are a manifestation of a central motivational state that is designed to promote recovery. Exaggerated symptoms of sickness in cancer patients, such as cachexia, can be life-threatening. However, quality of life is often drastically impaired before the cancer becomes totally debilitating. Although basic studies in psychoneuroimmunology have defined proinflammatory cytokines as the central mediators of sickness behavior, a much better understanding of how cytokine and neurotransmitter receptors communicate with each other is needed. Advances that have been made during the past decade should now be extended to clinical studies in an attempt to alleviate sickness symptoms and improve quality of life for cancer patients.

Inhibition of growth by pro-inflammatory cytokines: an integrated view.

Abstract: In response to antigenic stimuli, a variety of cells, including activated macrophages, secrete cytokines that are responsible for altering the host's metabolism. Three of these cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin-1 [IL-1], and interleukin-6 [IL-6]) have profound behavioral, neuroendocrine, and metabolic effects. There is evidence that cytokines and their cognate receptors are present in the neuroendocrine system and brain. Moreover, in laboratory animal species, IL-1, IL-6, and TNF-alpha have been found to modulate intermediary metabolism of carbohydrate, fat, and protein substrates, regulate hypothalamic-pituitary outflow, and act in the brain to reduce food intake. Finally, many of the systemic acute-phase responses to inflammatory stimuli such as lipopolysaccharide are inhibited by treatment with cytokine receptor antagonists. In short, many findings converge to suggest that a major component of the growth inhibition observed in immunologically challenged animals is mediated by pro-inflammatory cytokines. The goal of this article is to provide an integrated view of how cytokines act systemically on disparate tissues to alter growth.

Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system.

Abstract: Acute cognitive disorders are common in elderly patients with peripheral infections but it is not clear why. Here, we injected old and young mice with Escherichia coli lipopolysaccharide (LPS) to mimic an acute peripheral infection and separated the hippocampal neuronal cell layers from the surrounding hippocampal tissue by laser capture microdissection and measured mRNA for several inflammatory cytokines (IL-1β, IL-6, and TNFα) that are known to disrupt cognition. The results showed that old mice had an increased inflammatory response in the hippocampus after LPS compared to younger cohorts. Immunohistochemistry further showed more microglial cells in the hippocampus of old mice compared to young adults, and that more IL-1β-positive cells were present in the dentate gyrus and in the CA1, CA2, and CA3 regions of LPS-treated old mice compared to young adults. In a test of cognition that required animals to effectively integrate new information with a preexisting schema to complete a spatial task, we found that hippocampal processing is more easily disrupted in old animals than in younger ones when the peripheral innate immune system is stimulated. Collectively, the results suggest that aging can facilitate neurobehavioral complications associated with peripheral infections probably by allowing the over expression of inflammatory cytokines in brain areas that mediate cognitive processing.

From inflammation to sickness and depression: when the immune system subjugates the brain

Abstract: In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

Obesity induces a phenotypic switch in adipose tissue macrophage polarization

Abstract: Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.

Neuroinflammation in Alzheimer's disease

Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.