O desamparo do paciente sob a égide do terapeuta

O sentimento de desamparo faz parte da condição humana. O presente trabalho apresenta, através de casos clínicos, formas de comunicações das angústias de pacientes em psicoterapia e suas vivências sofridas, relacionando estas à importância do papel desenvolvido pelo terapeuta. Entendemos que é sob a égide deste que o paciente poderá experimentar-se, numa aventura a dois, reeditar relações anterior e arcaicamente “fracassadas” e, talvez assim, dar-lhes um novo sentido. É através desta relação que se abre uma porta para compreender melhor o estado de desamparo vivido pelo paciente; o terapeuta será aquele que irá amparar e proporcionar um espaço para que ocorra compreensão interna do desamparo sofrido.(AU)

The abandonment feeling is part of human condition. This work presents, through clinical cases, ways patients under psychotherapy communicate anguish and their suffered experiences, relating these to the importance of the role developed by the therapist. We understand that it is upon the therapist’s patronage that the patient will be able to experience himself, in a one-to-one adventure, re-edit prior failed liaisons and, maybe then, give them a new judgment. It is through this relationship that a path is created to better comprehend the abandonment condition lived by the patient, the therapist is the one who will patronize and provide room to let inner comprehension of all suffered abandonment happen.(AU)

Physiological significance of the interleukin 1 receptor accessory protein.

Interleukin 1 receptor accessory protein (IL-1RAcP) is an essential signal-transducing component of the IL-1 receptor type I. The recent availability of IL-1RAcP-deficient (KO) mice allows to study the in vivo function of IL-1RAcP. Animals were injected intraperitoneally with rat recombinant IL-1beta (200 ng/mouse), lipopolysaccharide (LPS, 5 microg/mouse), or subjected to 1-hour restraint stress. Neuroendocrine and immune parameters were measured 2 h after IL-1 or LPS injection or just after restraint. In wild-type controls, IL-1 and LPS activated the hypothalamic-pituitary-adrenal axis and increased plasma IL-6. In KO mice, the plasma levels of corticosterone and IL-6 increased after LPS, but not after rat recombinant IL-1beta. The LPS-induced depression of the lymphoproliferation was similar in wild-type and KO mice. Finally, the 1-hour restraint was able to increase the plasma levels of corticosterone in KO mice. These results show that IL-1RAcP is essential for physiological activities of peripheral IL-1, as it was previously demonstrated for those of brain IL-1. However, using IL-1RAcP KO mice, we were unable to demonstrate a specific role of endogenous IL-1 during LPS-induced inflammation. Moreover, stress-induced activation of the hypothalamic-pituitary-adrenal axis may occur in the absence of the IL-1-transducing receptor, IL-1RAcP.

Interleukin 1 receptor accessory protein (IL-1RAcP) is necessary for centrally mediated neuroendocrine and immune responses to IL-1beta.

Mice deficient for the IL-1RAcP gene (IL-1RAcP KO) were used to explore the role of IL-1RAcP in physiological functions of brain IL-1beta. Animals were injected i.c.v. with two different doses of recombinant human (rh) IL-1beta: a small one (750 pg) known to induce sickness behavior, and a larger one (50 ng), chosen to counteract the possible loss of affinity of IL-1beta on its receptor. Neuroendocrine and immune parameters were measured 2 h after IL-1 injection. The increase of plasma corticosterone induced by rhIL-1beta in wild-type (WT) mice was not observed in IL-1RAcP KO mice. Likewise, the depression of splenocyte proliferation occurred in WT but not in KO mice. Finally, in opposition to WT mice, plasma levels and brain cortical content of IL-6 in IL-1RAcP KO mice remained unchanged as compared to saline-injected controls. The results clearly demonstrate that IL-1RAcP is necessary for the induction of the main neuroendocrine and immune effects of central IL-1beta.

Influence of gender and behavioural lateralisation on two exploratory models of anxiety in C3H mice.

Behavioural lateralisation, which has been postulated to be an individual personality trait, is related to the activity of various physiological systems including the immune system. As lateralisation has been related to anxiety, which is known to influence immune reactivity, it can be hypothesized that the relation between lateralisation and immune reactivity involves individual behavioural patterns as they appear in exploratory-based anxiety models. In order to answer this question, a behavioural investigation focussing on exploratory activity was undertaken in male and female C3H mice previously selected for their paw preference. The observations were performed using two generic paradigms: elevated plus-maze and open field. Exploratory behaviour in the open field, but not in the plus-maze, was influenced by the interactive effect of gender and behavioural lateralisation. A significant difference between male and female mice was found in left-pawed but not in right-pawed nor ambidextrous animals, left-pawed female mice displaying the less exploratory behaviours. These results provide a first evidence of inter-individual variations in exploratory behaviours involving interaction between gender and lateralisation.

Strain-dependent association between lateralization and lipopolysaccharide- induced IL-1beta and IL-6 production in mice.

OBJECTIVE: The brain modulates the immune system in an asymmetrical way, as shown by the association between paw preference and immune response in the mouse. We predicted that the production of cytokines, which are one of the molecular pathways for brain-immune interactions, should be linked to lateralization in a strain-dependent manner. METHODS: We therefore measured plasma levels of interleukin (IL)-1beta and IL-6 after an intraperitoneal injection of lipopolysaccharide (LPS) in two strains of mice (C3H and BALB/c) that were selected for their different profiles of cytokine production. RESULTS: Plasma levels of IL-1beta and IL-6 increased after LPS injection in both strains and this increase was dependent on paw preference in BALB/c but not in C3H mice. Increased levels of IL-1beta were observed in left-pawed and ambidextrous but not in right-pawed mice. For IL-6, the LPS-induced increase was higher in ambidextrous than in left- and right-pawed animals. CONCLUSION: Cytokines may represent one of the factors responsible for interindividual differences in brain-immune interactions.

Activation of the hypothalamic-pituitary-adrenal axis in IL-1 beta-converting enzyme-deficient mice.

Interleukin-1beta (IL-1beta) plays a key role in immune, behavioral and neuroendocrine responses to inflammation or infection. IL-1beta could also be involved in the response of the hypothalamic-pituitary-adrenal (HPA) axis during stress. Mature IL-1beta derives from a 31-kD precursor (pro-IL-1beta) that is processed by IL-1beta-converting enzyme (ICE). Mice in which the ICE gene has been nullated by homologous recombination were used to investigate the role of IL-1beta in the HPA axis response. Plasma levels of corticosterone and adrenocorticotropic hormone (ACTH) in response to an intraperitoneal injection of 5 microg lipopolysaccharide (LPS) were similar in ICE-deficient mice and wild-type (WT) controls. In contrast, plasma ACTH response to restraint or to 200 ng of rat recombinant IL-1beta (rrIL-1beta) was higher in ICE-deficient mice as compared to WT animals. This hyperreactivity of the HPA axis in ICE knockout mice appears not to be related to the production of plasma IL-1beta or IL-6, which was similar to that of WT mice after rrIL-1beta injection. After lipopolysaccharide, ICE-deficient mice exhibited a smaller increase in plasma-immunoreactive IL-1beta and IL-6 as compared to WT controls. After restraint stress neither increase in plasma IL-1beta nor IL-6 was observed. The mechanisms responsible for the increased reactivity of the HPA axis in ICE-deficient mice may result from a higher sensitivity of the HPA axis to inflammatory cytokines or to cleavage products of pro-IL-1beta processed by non-ICE proteases.

Plasma corticosterone and immune reactivity in restrained female C3H mice.

Psychological stressors are known to stimulate the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system resulting in the release of corticosterone and catecholamines respectively. They have also been reported to induce cytokine production. All these molecules affect various immune parameters and can alter overall immune competence of the individual. The purpose of this investigation was to study the regulation of the production of corticosterone during stress and its possible effects on immune reactivity. In a first series of experiments, the possible regulation of corticosterone production by interleukin (IL)-1beta and peripheral catecholamines during restraint was assessed using a pharmacological approach in mice. Plasma IL-1beta concentrations remained at basal after 1-h restraint and the stress-induced increase of plasma corticosterone was not modified by a peripheral injection of an IL-1 receptor antagonist (IL-1ra). By contrast, chemical sympathectomy potentiated the restraint-induced increase in plasma corticosterone concentration, this potentiation being reversed by IL-1ra. In a second series of experiments, the role of corticosterone in stress-immune relationships was studied in adrenalectomized mice subjected to restraint and immunized with sheep erythrocytes. Non-specific immunity, i.e. proliferation of splenocytes and thymocytes and plasma levels of IL-1beta, as well as specific immunity, i.e. antibody production and delayed hypersensitivity, were not altered after 2-h restraint. Adrenalectomy failed to induce immune effects in stressed animals, except that delayed hypersensitivity was stronger in adrenalectomized animals, revealing that the high levels of corticosterone produced during stress have an anti-inflammatory activity. The present data show that the stress-induced production of corticosterone was modulated by both peripheral catecholamines and IL-1beta. However, this production of corticosterone was unable to modulate immune reactivity except delayed hypersensitivity.

Mechanisms of behavioral and neuroendocrine effects of interleukin-1 in mice.

Interleukin-1 beta is a key molecule in brain-immune interactions that, apart from its immune effects, stimulates the hypothalamo-pituitary-adrenal (HPA) axis and induces behavioral alterations. However, its physiological role during stress responses remain to be elucidated. The possible mechanisms involved in IL-1-mediated stimulation of the HPA axis during stress were assessed by using different approaches. They were first studied in mice deficient for the IL-1 beta-converting enzyme (ICE) gene. Mature IL-1 beta derives from a precursor, the pro-IL-1 beta, devoid of any conventional signal sequence that is mainly processed by ICE. After immune or stress stimulation, ICE-deficient mice were shown to have a hyperactive HPA axis and to able to produce immunoreactive IL-1 beta. This indicates that the greater reactivity of the HPA axis could result from a higher sensitivity to non-ICE-matured IL-1 beta, as suggested by a higher basal transcription of hypothalamic IL-1 receptor type I (IL-1 RI) in ICE-deficient mice. The biological effects of IL-1 beta are mediated by IL-1 RI associated with the IL-1 receptor accessory protein (IL-1RAcP). IL-1RAcP is an essential component for IL-1 action at the periphery, but its role in the brain is not well known. Therefore, the effects of i.c.v. IL-1 beta were studied in IL-1RAcP-deficient mice. In normal mice, i.c.v. IL-1 beta depresses peripheral immune responses, induces the production of plasma IL-6, and stimulates the HPA axis. None of these effects were observed in IL-1RAcP-deficient mice, indicating that IL-1RAcP is necessary for the induction of the main neuroendocrine and immune effects of central IL-1 beta. In normal mice, the role of IL-1 beta was assessed by pretreating the animal with the IL-1 receptor antagonist (IL-1Ra). IL-1Ra did modify the activation of the HPA axis observed during stress, except when the animals were previously sympathectomized. This suggests that the sympathetic nervous system can downregulate the IL-1 beta-induced stimulation of the HPA axis. Finally, the modulation of the production and physiological activities of IL-1 were studied in normal mice, taking advantage of interindividual differences in brain-immune interactions linked to cerebral lateralization. Behavioral/brain lateralization was shown to be related to behavioral response to peripheral administration of IL-1, and to the production of IL-1 and IL-6 in response to LPS. This suggests that cytokines, and especially IL-1 beta, may represent one of the factors responsible for interindividual differences in brain-immune interactions.

Asymmetrical distribution of hippocampal mineralocorticoid receptors depends on lateralization in mice.

Previous experiments showed that the activation of the hypothalamic-pituitary-adrenal (HPA) axis during stress was associated with behavioral lateralization used as a marker of population heterogeneity in mice. Furthermore, brain asymmetries have been demonstrated in neurotransmitter metabolism and neuroendocrine modulation. As the hippocampus modulates the activity of the HPA axis in stress and basal conditions, we postulated that hippocampal corticoid receptors may be asymmetrically distributed and that asymmetry may differ according to behavioral lateralization of animals. In order to answer these questions, binding capacity of mineralocorticoid (MR) and glucocorticoid (GR) receptors was determined in right and left hippocampi of mice previously selected for paw preference. The results show that regardless of behavioral lateralization, there was a tendency for a right dominance in MR binding capacity in the hippocampus but interestingly, the percentage of right/ total MR binding capacity was inversely correlated with individual paw preference scores. The affinity of MRs did not depend on behavioral lateralization. GR binding capacity was similar in each hemisphere and no relationship was found between GR binding capacity and paw preference scores. These results suggest that hippocampal receptors for corticoids may play an important role in the asymmetrical brain control of immune reactivity.

Interleukin-1-induced sickness behavior depends on behavioral lateralization in mice.

Inter-individual differences in brain-immune interactions have been demonstrated previously in mice using lateralization as a behavioral trait of population heterogeneity. Lipopolysaccharide (LPS), which is known to induce neurochemical, neuroendocrine, and immune responses depending on lateralization, is also able to induce sickness behavior, via the production of interleukin-1 (IL-1). The objective of this study was to determine whether lateralization can influence the behavioral response to LPS and to IL-1. To test this hypothesis, adult female C3H mice, previously selected for paw preference in a food reaching task, were injected intraperitoneally (i.p.) with 0.75 microg LPS or 0.75 microg recombinant IL-1beta. Sickness induced by these molecules was measured by depressed social behavior, increased immobility, loss of body weight, and reduced food intake during the 6 h following injection. LPS-induced sickness was similar in right- and left-pawed mice. In contrast, IL-1-induced sickness behavior was dependent on behavioral lateralization. IL-1-induced depression of social investigation was more pronounced in right-pawed mice than in left-pawed animals. Likewise, IL-1-induced immobility was more important in right-pawed mice. There was a similar trend for food intake to be lower and loss of body weight to be higher in right-pawed mice than in left-pawed animals. These results demonstrate that right-pawed mice are more sensitive to IL-1-induced sickness than left-pawed animals. They extend our previous data showing a greater susceptibility to stress of right-pawed animals. The existence of inter-individual differences in the reactivity to stress or immune activation may be useful to study the mechanisms of the various strategies used by an individual in response to environmental aggressions.