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Acute-phase immune response: lipopolysaccharide-induced fever and sleep alterations are not simultaneously conditionable in the rat during the inactive (light) phase.

Recent research has demonstrated that specific parameters of the immune system can be augmented by behavioral conditioning. These physiological alterations have been largely achieved by implementation of the conditioned taste aversion paradigm. Fever and sleep alterations are early occurrences within the acute-phase immune response to infection. The present study attempted to concurrently condition these two simultaneous, yet independent, responses. Lipopolysaccharide (LPS) was used as an unconditioned stimulus. When paired with a novel-tasting saccharin solution, a conditioned febrile response was observed. However, the somnogenic effects of LPS were not simultaneously conditionable. The conditioning of fever, as well as other interleukin-1-mediated responses, offers promise in both clinical and experimental applications.

Acute-Phase Reaction↗

Risk taking, depression, adherence, and symptom control in adolescents and young adults with asthma.

Risk behaviors, including tobacco, alcohol, and drug use, are common in adolescents and young adults. Those who engage in one risk behavior are likely to engage in additional health risk behaviors, and as the number of risk behaviors increase, depression comorbidity emerges. For young people with chronic illness, risk behavior and depression are also common. There is some evidence that both depression and risk behavior are associated with nonadherence to medications, poor treatment outcomes, and death. The relationship between depression and asthma may involve more than one causal pathway and includes the possibility that depression can lead to a sense of hopelessness that erodes adherence and other health-promoting behavior, or that depression impacts asthma directly by altering the immune system. An assessment of the interplay between risk behavior, depression, adherence, and asthma can add important new information to our understanding about how to identify and treat those at greatest risk for poorly controlled disease and asthma-related death. New behavioral studies must overcome the shortcomings frequently seen in previous research and include well-designed and controlled investigations using valid behavioral measures of risk behavior, mood disorder, and adherence; recruitment that includes sufficient numbers of subjects and gives careful consideration of selection bias; and employment of multivariate data modeling to allow for simultaneous statistical examination of multiple relationships.

Adolescent↗

Clinical evaluation of patients with temporomandibular joint implants.

PURPOSE: An undetermined number of patients with temporomandibular joint (TMJ) symptoms have been treated with intra-articular disc implants composed of Teflon ethylene/propylene or Teflon polytetrafluoroethylene and aluminum oxide (Proplast-Teflon; Vitek, Houston, TX). These implants have shown the potential to fragment in situ resulting in nonbiodegradable particles that stimulate a giant cell reaction and lead to degeneration of local structures, pain, and limitation of mandibular opening. We examined the possible relationship between TMJ implants and persistent pain, responses to sensory stimuli, quality of life, and systemic immune dysfunction. PATIENTS AND METHODS: This case series (32 patients) were referred from university-based orofacial pain centers and private practices from across the United States. Laboratory and clinical assessments evaluated orofacial pain symptoms, neurologic function, clinical signs and symptoms of rheumatologic disease, physical function, systemic measures of immune function, and behavioral measures. RESULTS: We found that TMJ implant patients appeared to have altered sensitivity to sensory stimuli, a higher number of tender points with a diagnosis of fibromyalgia, increased self-report of chemical sensitivity, higher psychologic distress and significantly lower functional ability. Systemic illness or autoimmune disease was not evident in this series of TMJ implant patients. CONCLUSIONS: Significant problems were noted on clinical assessment of TMJ implant patients. This is a US government work. There are no restrictions on its use.

Adult↗

The immune system as a supersystem.

I coined a term "supersystem" to designate highly integrated life systems such as the immune system, nervous system, and embryogenesis. While the mechanistic system is defined as a set of diverse elements so connected and related as to form an organic whole for a particular purpose, the "supersystem" engenders its own elements from a single progenitor. The diverse elements thus generated form relationship by mutual adaptation and coadaptation, and thus they create a dynamic self-regulating system through self-organization. It is a closed self-satisfied system, yet open to the environment, receiving outside signals to transduce them into internal messages for self-regulation and expansion. Unlike a mechanistic system, the "supersystem" has no defined purpose and determines its own fate by referring to its self-established behavioral pattern. Both the immune and nervous systems develop and function as a typical "supersystem." The prototype of the supersystem can be seen in embryogenesis and evolution. The concept of the supersystem can also be applied to the development of language, or a city, or other cultural phenomena that human beings have created as a result of their vital activities.

Activins↗

Behavior, reproduction, and immunity of crated pregnant gilts: effects of high dietary fiber and rearing environment.

The objective of this study was to examine effects of increased gut fill and diverse developing environments on pregnant gilts' behavior and physiology. Gilts were cross-fostered at 1 d of age and transferred to either an indoor or outdoor production unit. Littermate gilts remained in their different environments during development and were moved into individual gestation crates in an indoor gestation unit. Of the 42 gilts, 19 were fed a control diet of fortified sorghum-soybean meal and 23 were fed the same diet with 25% beet pulp (high fiber). Control sows ate 2.0 kg/d and high-fiber sows ate 2.67 kg/d in a large pellet (thus resulting in approximately equal energy intake and differing total dietary intakes). Pregnant gilts had behavior and immune measures sampled at 30, 60, and 90 d of gestation. The day x diet interaction was significant (P = 0.01) for duration of standing: sows fed high-fiber diets stood less on d 30, but on d 60 and 90 they and the control sows stood for a similar duration. Sham chewing duration and frequency showed significant (P < 0.05) effects of gestation stage x diet x environment. Gilts reared outdoors and fed high fiber increased sham chewing over gestation, whereas all other treatment groups decreased this behavior over time. Outdoor-reared gilts had greater (P < 0.05) frequency and duration of drinking behavior than indoor-reared gilts. White blood cell numbers were higher (P < 0.05) for gilts fed high-fiber diets than for gilts fed the control diet. Immune (humoral and cellular systems) and reproductive measures (farrowing rate and litter size) and plasma cortisol concentrations were generally not influenced (P > 0.10) by diets and rearing environments, suggesting that in spite of significant changes in behavior and feed intake gilts' immune systems were not suppressed or enhanced. Behavioral data alone suggested that indoor-reared gilts showed fewer behavioral adaptations to the crates than outdoor-reared gilts. However, immune measures did not indicate that any treatments resulted in physiological effects indicative of stress.

Animals↗

On the development of psychoneuroimmunology.

Psychoneuroimmunology, the study of interactions among behavioral, neural and endocrine, and immune processes, coalesced as an interdisciplinary field of study in the late 1970s. Some of the early research that was critical in establishing neuroanatomical, neurochemical and neuroendocrine pathways and functional relationships between the brain and the immune system is outlined here. These and subsequent studies have led to the general acknowledgment that the nervous and immune systems are components of an integrated system of adaptive processes, and that immunoregulatory processes can no longer be studied as the independent activity of an autonomous immune system. This paradigm shift in the study of immunoregulatory processes and the elaboration of the mechanisms underlying behaviorally induced alterations of immune function promise a better understanding and a new appreciation of the multi-determined etiology of pathophysiological states.

Animals↗

Influence of stressor predictability and behavioral control on lymphocyte reactivity, antibody responses and neuroendocrine activation in rats.

The present experiments were designed to study the influence of prediction and control of electric shocks on various aspects of immune function, and the possible intermediate role of glucocorticoid hormones. After two sessions of inescapable footshocks, the reactivity of splenocytes to concanavalin A was reduced by one third. This effect was completely reversed when each shock was preceded by a warning stimulus, even though the adrenocortical response was the same in both conditions. In another experiment, rats were submitted to ten sessions of continuous avoidance in a shuttle-box and a group of yoked animals received the same footshocks without any relationship to their shuttling behavior. Although yoked rats displayed a reduced reactivity of splenocytes to lectins, animals of the avoidance group had a reduced antibody response to sheep erythrocytes. In contrast, no difference was observed in the corticosterone or prolactin response. These data further support the importance of psychological factors on stress-induced changes in immune functions. Furthermore, they demonstrate that various aspects of the immune system are differentially affected by behavioral factors and the results argue against a major role for the adrenocortical system in mediating these changes.

Adaptation, Psychological↗

[Communicative behavioral effects and disorders of immunity].

Rats and mice subjected to stress and/or irradiation or their urine induce impairment or the indices of immunologic reactivity in caged together their intact mates. It is suggested that communicative behavior, including olfactory-odor components, affect the state of blood and immunity systems.

Animals↗

Bidirectional communication between the brain and the immune system.

There is now a substantial body of data available indicating that the brain, the nervous system, and the immune system are functionally connected. Consequently, environmental conditions of a psychosocial or physical nature may influence the body's defence. The magnitude of the change in immune reactivity is partly determined by the individual's evaluation of the psychological or physical stimulus. This is illustrated by pharmacological modification of perception resulting in more pronounced stress-induced immunomodulation. In man, it has been demonstrated that recently experienced life stress, particularly daily hassles, can codetermine the effect of an experimental stressor applied for a short period of time on the immune system. An intriguing finding relates to the synthesis and secretion of hormones and neuropeptides by immune cells. These chemical messengers act as autocrine or paracrine immunoregulatory molecules on the one hand, and as messengers for communication with the brain and peripheral nervous system on the other. Animal research indicates that this dialogue is of biological significance.

Animals↗

Ghrelin, the same peptide for different functions: player or bystander?

Ghrelin is a recently discovered brain-gut peptide with two main physiological actions: growth hormone secretagogue activity and food intake inducer. Although its production is prevalently gastric, ghrelin is widely expressed in several tissues, where it might therefore act as a paracrine or autocrine factor. It is becoming clear that ghrelin is much more than a simple growth hormone secretagogue. In addition to its formerly envisaged role, ghrelin has other activities including stimulation of pituitary hormones secretion, modulation of food intake and control of energy metabolism, regulation of gastric and pancreatic activity, and cardiovascular and hemodynamic activities. In addition, modulation of cartilage and bone homeostasis, sleep and behavioral influences, and modulation of the immune system, as well as effects on cell proliferation, are other relevant actions of ghrelin. Thus, the peptide appears to be an important component of an integrated multifaceted regulatory system. In this review, we summarize several aspects of ghrelin biology and attempt to inform the reader with information regarding unexpected functions of this gastric peptide.

Acylation↗

Food handling behaviors of special importance for pregnant women, infants and young children, the elderly, and immune-compromised people.

This study used a Web-based Delphi process with a group of nationally recognized food safety experts to identify food-handling behaviors of special importance in reducing the risk of foodborne illness among pregnant women, infants and young children, elderly people, and people with compromised immune systems because of disease or pharmacologic therapy. Behaviors were related to 13 pathogens. Top-rated behaviors for pregnant women were associated with Listeria monocytogenes, Toxoplasma gondii, and Salmonella species. Top-rated behaviors for infants and young children, elderly people, and immune-compromised people were associated with a number of different pathogens. The results should help dietetics professionals and community health educators focus their efforts on those behaviors of special importance to the population being targeted.

Age Factors↗

The neuroimmunology of stress and depression.

This article reviews evidence that shows a bidirectional relationship between the brain and the immune system. As a result of this relationship, mental factors such as stress and depression have been shown to affect immune system functioning, with both immunosuppression and immune activation being reported. Stress and depression also have been associated with worse outcomes in immune-related disorders including cancer and infectious diseases suggesting that stress/depression effects on the immune system are clinically relevant to disease expression. Conversely, several lines of evidence suggest that immune system activation such as during infectious diseases, cancer, and autoimmune disorders is associated with the development of behavioral symptoms similar to those seen in the context of chronic stress or major depression. These findings implicate a role for the immune system in the cause of behavioral disorders in a wide range of medical illnesses. Finally, a paradigm is proposed in which abnormal functioning of either the hypothalamic-pituitary-adrenal (HPA) axis or the inflammatory response system disrupts feedback regulation of both neuroendocrine and immune systems contributing to the development of neuropsychiatric and immunologic disorders.

Brain↗

Behavioral adaptations to parasites: an ethological approach.

Wild vertebrate animals must live in an environment with the ever present threat of internal and external parasites. This threat by macroparasites is responsible for the natural selection of an array of behavioral adaptations that, together with the immune system and other physiological forms of resistance, enable the animals to survive and reproduce in this environment. Several lines of research, some quite recent, illustrate that specific behavioral patterns can be effective in helping animals or their offspring avoid or control macroparasites that can affect adversely the animal's fitness. These behavioral patterns fall under the general strategies of avoidance behavior and mate selection.

Animals↗

Immune responses following competitive water tests in two species of macaques.

A panel of immune parameters (lymphocyte activation by mitogens, natural cytotoxicity, and differential cell counts) was assessed in socially housed pigtail and bonnet macaques 1 and 2 weeks before, 48 h after, and 1 and 2 weeks after a competitive water test. Species differences were found in both baseline measures and the responses to the test: Immune measures observed during baseline periods were lower in pigtail macaques. Furthermore, only the pigtail macaques showed changes in mitogen activation and cytotoxicity at 48 h post-test. Dominance-related behaviors affected these responses both within and across social groups. The species differences may be accounted for by the differences in the behavioral responses of the two species to the test: Pigtail macaques consistently contested access to the water during the test, whereas bonnet macaques did not. These results suggest that the immune system can be modulated by psychosocial behavioral systems, particularly during times of stress.

Animals↗

Manipulation of behavioral disorders in autoimmune mice via prolactin.

Autoimmune mice perform poorly in two-way active avoidance tasks, and the extent of this performance deficit appears to be related to the extent of autoimmunity following developmental manipulations. In the current study, the pituitary hormone prolactin, which has immune-enhancing effects, was used to manipulate this behavioral disorder in adulthood. Prolatinergic manipulation may be achieved by the use of dopaminergic drugs. In two experiments, autoimmune NZB X NZW F1 (BW) mice received either pimozide (PIM; a D2 antagonist) or bromocriptine (CB154; a dopamine agonist) in their drinking water. Control subjects received plain water. Following treatment, subjects were tested in an activity monitor, and active avoidance learning. Circulating PRL levels, as measured by RIA, were significantly increased by PIM and significantly decreased by CB154. Neither drug affected circulating levels of autoantibodies to DNA or cardiolipin, a phospholipid. In Experiment 1, in which mice were tested at 12 weeks of age, after 6 weeks of drug treatment, PIM treated animals of both sexes showed significantly more failures to escape the shock in avoidance conditioning, while CB154 did not have significant effects. In Experiment 2, in which mice were tested at 16 weeks of age, after 12 weeks of drug treatment, CB154 treated females (males were not tested) showed significantly fewer failures to escape, while PIM did not have significant effects. The effects of PRL on behavior, and its relation to immune system function, are discussed.

Animals↗

Variant exons v6 and v7 together expand the repertoire of glycosaminoglycans bound by CD44.

Isoforms of the glycoprotein CD44 are cell surface receptors for the glycosaminoglycan hyaluronate. They have been implicated in many biological processes, but their function in these is poorly understood and cannot be explained solely by hyaluronate binding. In the present work we examine the ligand binding properties of alternatively spliced CD44 variant isoforms which are functionally involved in the immune system, embryonic development, and tumor behavior. We show that these isoforms bind directly to the purified glycosaminoglycans chondroitin sulfate, heparin, and heparin sulfate, in addition to being able to bind to hyaluronate. Binding to this extended repertoire of glycosaminoglycans by CD44 depends on the inclusion of peptide sequences encoded by the alternatively spliced exons v6 and v7, and occurs both when the CD44 is solubilized from the plasma membrane and when it is expressed on intact cells. A single point mutation in the most N-terminal hyaluronate binding motif of CD44 ablates both hyaluronate and chondroitin sulfate binding, suggesting that glycosaminoglycans are bound through a common motif, and that only one of the hyaluronate binding motifs is responsible for the majority of glycosaminoglycan binding by CD44 on the cell surface. Taken together, these observations indicate that alternative splicing regulates the ligand binding specificity of CD44 and suggest that structural changes in the CD44 protein have a profound effect on the range of ligands to which this molecule can bind with potentially wide-ranging functional consequences.

Alternative Splicing↗

Immunity, neuroglia and neuroinflammation in autism.

Autism is a complex neurodevelopmental disorder of early onset that is highly variable in its clinical presentation. Although the causes of autism in most patients remain unknown, several lines of research support the view that both genetic and environmental factors influence the development of abnormal cortical circuitry that underlies autistic cognitive processes and behaviors. The role of the immune system in the development of autism is controversial. Several studies showing peripheral immune abnormalities support immune hypotheses, however until recently there have been no immune findings in the CNS. We recently demonstrated the presence of neuroglial and innate neuroimmune system activation in brain tissue and cerebrospinal fluid of patients with autism, findings that support the view that neuroimmune abnormalities occur in the brain of autistic patients and may contribute to the diversity of the autistic phenotypes. The role of neuroglial activation and neuroinflammation are still uncertain but could be critical in maintaining, if not also in initiating, some of the CNS abnormalities present in autism. A better understanding of the role of neuroinflammation in the pathogenesis of autism may have important clinical and therapeutic implications.

Animals↗

The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures.

Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range of neurological consequences, some of which were headache, general debilitating pains, fever, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, and seizures.

Environmental Exposure↗