Psychosocial stress and inflammation in cancer.

Stress-induced immune dysregulation results in significant health consequences for immune related disorders including viral infections, chronic autoimmune disease, and tumor growth and metastasis. In this mini-review we discuss the sympathetic, neuroendocrine and immunologic mechanisms by which psychosocial stress can impact cancer biology. Both human and animal studies have shown the sympathetic and neuroendocrine responses to psychosocial stress significantly impacts cancer, in part, through regulation of inflammatory mediators. Psychosocial stressors stimulate neuroendocrine, sympathetic, and immune responses that result in the activation of the hypothalamic-pituitary-adrenal (HPA)-axis, sympathetic nervous system (SNS), and the subsequent regulation of inflammatory responses by immune cells. Social disruption (SDR) stress, a murine model of psychosocial stress and repeated social defeat, provides a novel and powerful tool to probe the mechanisms leading to stress-induced alterations in inflammation, tumor growth, progression, and metastasis. In this review, we will focus on SDR as an important model of psychosocial stress in understanding neural-immune mechanisms in cancer.

Alleviation of the effects of endotoxin exposure on behavior and hippocampal IL-1beta by a selective non-peptide antagonist of corticotropin-releasing factor receptors.

Previous research has shown that lipopolysaccharide (LPS) or interleukin-1beta (IL-1beta) administration produces learning/memory deficits in a variety of paradigms. In our laboratory, we have consistently observed LPS-induced behavioral alterations in a two-way active avoidance conditioning paradigm. Following LPS administration, one factor that affects cytokine production is corticotropin-releasing factor (CRF). CRF has well known anti-inflammatory effects, via stimulation of ACTH and corticosterone release. However, CRF acting directly on immune cells or within the CNS may potentiate proinflammatory effects. The current experiments explored the potential of antalarmin, a CRF-R1 non-peptide antagonist, to diminish or negate deficits observed with LPS administration. On the first day of testing, four-month-old male C57BL/6J mice received an intraperitoneal (i.p.) injection of antalarmin, followed 90min later by a second i.p. injection of LPS 4h prior to two-way active avoidance conditioning testing. As hypothesized, LPS administration altered performance. However, pretreatment with antalarmin attenuated the adverse effects of LPS administration. Moreover, evidence indicates that antalarmin attenuated hippocampal, but not peripheral, cytokine release. The behavioral results cannot be explained by alterations in the HPA axis, as antalarmin did not affect the LPS-induced rise in corticosterone. The current research contributes preliminary evidence that CRF may be an important factor in the development of LPS-induced behavioral effects, and that blocking the activity of CRF may be sufficient to alleviate some of the effects of endotoxin exposure, possibly due to diminished LPS-induced IL-1beta release in the dorsal hippocampus.