Influence of interleukin-1β on exploratory behaviors, plasma ACTH, corticosterone, and central biogenic amines in mice

Abstract

Systemic administration of interleukin-1beta (IL-1beta) promoted behavioral changes in an open-field exploratory test. In particular, while the cytokine suppressed locomotor activities, these behaviors were not particularly sensitive to dosage differences. In contrast, dose-dependent biphasic variations that varied over time were evident with respect to the exploration of a novel container. Within this paradigm, the behavioral changes did not appear to be related to neophobia. In addition, despite the marked effects of IL-1beta on exploratory and locomotor behaviors, habituation/exploration in a free-running spontaneous alternation task was unaffected by the cytokine. In addition to the behavioral variations, IL-1beta dose-dependently increased plasma ACTH and corticosterone concentrations, and also induced several central monoamine alterations. In particular, IL-1beta increased the utilization of norepinephrine (NE) within the paraventricular nucleus, arcuate nucleus/median eminence, locus coeruleus, and prefrontal cortex, while the turnover of dopamine (DA) was evident in the arcuate nucleus/median eminence. It is suggested that although systemic IL-1beta treatment induces some stress-like effects, the profile of central neurochemical changes induced by the cytokine can be distinguished from psychological or processive types of stressors.

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

“…37,46 Changes in open-field behavior have also been documented in animals administered cytokines in isolation, including TNFalpha and IL-1 and in animals with relevant cytokine genes deleted or overexpressed. 23,[39][40][41][42][47][48][49] Taken together with our results, these findings support the notion that cytokines released during immune activa- were measured over 5 min in ADX WT or TNF-R1-KO mice (n = 5-10 animals per group). Data were analyzed by a twoway ANOVA, and group differences were assessed using the Student-Newman-Keuls post hoc test of significance.…”

“…57,58 In addition, as noted above, TNFalpha effects may be mediated by induction of downstream cytokines such as IL-1, which has been shown to have a behavioral profile similar to TNFalpha in open-field testing. [40][41][42] Finally, consideration should be given to the possibility that reduced host responses to viral infection in TNF-R1-KO mice may be responsible (in relatively non-specific fashion) for the reversal of anxiety-like behaviors in glucocorticoid-deficient, MCMV-infected animals. As mentioned previously, TNF-R1-KO mice have been shown to exhibit reduced host responses.…”

“…Indeed, as noted above, IL-1 has been shown to reduce locomotor activity both alone and in combination with IL-6. [40][41][42]60 Given the critical role played by glucocorticoids in regulating immune responses (especially restraining inflammatory responses), patient populations with altered glucocorticoid signaling as result of reduced hormone or reduced glucocorticoid receptor expression/function, including post-traumatic stress disorder (PTSD) and major depression, may be especially vulnerable to the pathological/behavioral consequences of prolonged exposure to elevated circulating levels of proinflammatory cytokines. Indeed, both of these disorders have been found to be associated with an exaggerated inflammatory responses including increases in plasma concentrations of TNF-alpha and IL-6, and both are associated with increased symptoms of anxiety and alterations in locomotor activity, including psychomotor slowing and fatigue.…”

“…32,33 Moreover, open-field behavior has been shown to be altered in cytokine-treated and infected animals as well as animals with autoimmune disease. 21,28,[34][35][36][37][38][39][40][41][42] In addition, since TNF-alpha has been demonstrated to mediate MCMV-induced consequences on survival, we examined the possibility that TNF-alpha might also contribute to behavioral alterations in MCMV-infected animals. To abrogate TNF-alpha activity, TNF-alpha receptor 1 (TNFRp55) knockout (TNF-R1-KO) mice were employed.…”

Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder

“…IL-1 beta has been shown to modulate the release of dopamine and norepinephrine in several brain regions. 5 Genetic variability in central modulation of monoamine activity may be relevant to the phenotypic expression of ADHD symptomatology. A polymorphic site with five allelic variants comprising of two to six copies of an 86-base pair tandem repeat, has been described in the second intron of the gene encoding IL-1Ra.…”