Neurohormonal Host Defense in Endotoxin Shock

Abstract

Lipopolysaccharide (LPS) of gram-negative bacteria is capable of activating the immune system of higher animals, which may lead to cytokine-induced lethal shock and death. LPS has little toxicity for the frog and fish, but it kills the horseshoe crab instantly by causing intravascular blood coagulation. The response to LPS evolved from simple reactions in lower animals into an intense reaction in mammals that involves a massive immune activation leading to a profound neuroendocrine and metabolic response. This is now known as the acute-phase response (APR). During APR, LPS-binding proteins (LBP) are produced by the liver in rapidly increasing quantities under the influence of interleukin-6, glucocorticoids, and catecholamines. After combination with LPS, LPB is capable of activating monocyte-macrophages and granulocytes via the CD14 surface receptor. Other receptors (CD18, 80-kDa receptor) allow for direct action by LPS of phagocytes, B and T lymphocytes, and other cells. Numerous other acute-phase proteins are produced in the liver, including C-reactive protein, complement components, fibrinogen, enzyme inhibitors, and anti-inflammatory proteins. Similar responses may be stimulated by subtoxic doses of LPS or by detoxified LPS, which manifest in endotoxin tolerance. Tolerant animals and man show increased resistance to LPS, to infections, and to various noxious insults. Infection and various forms of tissue injury are also capable of causing APR. There is much evidence to indicate that APR, which manifests in febrile illness, is an efficient host defense reaction. It is an emergency response in cases where specific immunity fails to protect the host. Therefore, the neuroimmunoregulatory network converts the immune system to a less specific, but rapid and more efficient response, APR. The hypothesis is presented that intestinal LPS serves to amplify the APR in response to various insults, which contribute to host defense, regeneration, and healing.

Review: Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis

“…44,58,109,265 Thus, HPA activation in response to LPS challenge is thought to be an important adaptive immunoregulatory response, suppressing inflammatory response by dampening production of acute-phase proteins and pro-inflammatory cytokines, and thereby preventing septic shock. 266 In addition, CRH receptor-independent mechanisms are operative in the immune stimulation of the HPA axis. [267][268][269] In patients with sepsis, a dissociation of the HPA axis has been observed in the course of their illness, suggesting a loss of the feedback of the HPA axis.…”

Lipopolysaccharide facilitates partner preference behaviors in female prairie voles

“…This involvement suggests a possible mechanism through which pair bonding may be rewarding. Furthermore, LPS significantly increases the release of the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) from the posterior pituitary gland in rats [39][40][41], and there are high densities of OT receptors in the prelimbic cortex and nucleus accumbens of prairie voles, which are regions involved in the dopamine mesolimbic reward pathway [36]. A number of studies have implicated the involvement of OT and AVP in the mediation of complex social behaviors such as affiliation and parental care in prairie voles, as well as in the facil- itation of the consolidation of memory of socially familiar animals [20][21][22]34,36].…”

Role of Endothelial TLR4 for Neutrophil Recruitment into Central Nervous System Microvessels in Systemic Inflammation

“…Moreover, brain injury (1,2) and neurodegenerative diseases including Alzheimer's disease (3) and multiple sclerosis (4) could be significantly exacerbated by systemic infection. In animal experiments, systemic infection caused many physiological responses including changes in neuroendocrine and motor activity (5)(6)(7). Furthermore, systemic inflammation could also exacerbate brain inflammation (8) and increase neuronal death (9).…”