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Biomedical subjects

R Dantzer

Publications and source records attributed to R Dantzer.

240 records · Page 14Linked to original sources
PubMedDate not supplied

Timing and specificity of the cognitive changes induced by interleukin-2 and interferon-alpha treatments in cancer patients.

OBJECTIVE: Neuropsychological changes develop in patients treated by cytokine immunotherapy with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha). However, the time course of appearance of these effects remains unclear, and their precise nature is still incompletely characterized. The objective of this study was to assess and characterize the early cognitive changes induced by IL-2 and IFN-alpha in cancer patients at the end of the first week of treatment and to investigate the subsequent evolution of these changes. METHODS: The study was conducted in 47 cancer patients who received subcutaneous IL-2, administered alone (N = 17) or with IFN-alpha (N = 7), or IFN-alpha alone, administered subcutaneously at low doses (N = 7) or intravenously at high doses (N = 16). An automated battery of neuropsychological tests (Cambridge Neuropsychological Test Automated Battery) was used to measure reaction time, spatial working memory, and planning tasks. Cognitive tests were performed before treatment (day 1) and after 5 days (day 5) and 1 month of treatment. RESULTS: On day 5, patients treated with IL-2 alone had impaired spatial working memory and lower accuracy of planning abilities. In contrast, patients treated with IFN-alpha did not show any impairment in performance accuracy in these tasks but showed longer latencies in the test of reaction time. Most of these early alterations persisted at the end of the first month of treatment without any obvious sign of worsening. CONCLUSIONS: These findings suggest the existence of early differential neuropsychological changes in patients treated with IL-2 and IFN-alpha.

Adjuvants, Immunologic↗
PubMedDate not supplied

The immune-endocrine loop during aging: role of growth hormone and insulin-like growth factor-I.

Why a primary lymphoid organ such as the thymus involutes during aging remains a fundamental question in immunology. Aging is associated with a decrease in plasma growth hormone (somatotropin) and IGF-I, and this somatopause of aging suggests a connection between the neuroendocrine and immune systems. Several investigators have demonstrated that treatment with either growth hormone or IGF-I restores architecture of the involuted thymus gland by reversing the loss of immature cortical thymocytes and preventing the decline in thymulin synthesis that occurs in old or GH-deficient animals and humans. The proliferation, differentiation and functions of other components of the immune system, including T and B cells, macrophages and neutrophils, also demonstrate age-associated decrements that can be restored by IGF-I. Knowledge of the mechanism by which cytokines and hormones influence hematopoietic cells is critical to improving the health of aged individuals. Our laboratory has recently demonstrated that IGF-I prevents apoptosis in promyeloid cells, which subsequently permits these cells to differentiate into neutrophils. We also demonstrated that IL-4 acts much like IGF-I to promote survival of promyeloid cells and to activate the enzyme phosphatidylinositol 3'-kinase (PI 3-kinase). However, the receptors for IGF-I and IL-4 are completely different, with the intracellular beta chains of the IGF receptor possessing intrinsic tyrosine kinase activity and the alpha and gammac subunit of the heterodimeric IL-4 receptor utilizing the Janus kinase family of nonreceptor protein kinases to tyrosine phosphorylate downstream targets. Both receptors share many of the components of the PI 3-kinase signal transduction pathway, converging at the level of insulin receptor substrate-1 or insulin receptor subtrate-2 (formally known as 4PS, or IL-4 Phosphorylated Substrate). Our investigations with IGF-I and IL-4 suggest that PI 3-kinase inhibits apoptosis by maintaining high levels of the anti-apoptotic protein Bcl-2. The sharing of common activation molecules, despite vastly different protein structures of their receptors, forms a molecular explanation for the possibility of cross talk between IL-4 and IGF-I in regulating many of the events associated with hematopoietic differentiation, proliferation and survival.

Aging↗
PubMedDate not supplied

Environment and behaviour in husbandry.

The changes seen in animal behaviour are a measure of the reaction of the animal to a given environment: examples of them are found in husbandry, in connection with both social and physical factors of the environment. Disorders of behavior occurring in intensive farms pose still unresolved theoretical problems, especially in the realm of possible analogies with displacement activities. The control of behaviour reactions is possible by manipulating the environment, or the animals themselves, by genetic selection or by means of tranquillizers. A better knowledge of the effects of management methods on the behaviour of livestock is needed, however, especially if precise recommendations relating to animal welfare are to be formulated.

Adaptation, Physiological↗
PubMedDate not supplied

How do cytokines say hello to the brain? Neural versus humoral mediation.

Infection and inflammation are accompanied by fever, neuroendocrine activation and alterations in behaviour and mood. It is commonly accepted that these non specific symptoms are mediated by blood-borne mediators acting on the brain. These mediators include proinflammatory cytokines such as IL-1, IL-6 and TNF. In this paper, we present new evidence indicating that this view is inadequate and that the proinflammatory cytokines which are released at the periphery by activated accessory immune cells act on the brain via a neural pathway involving activation of peripheral sensory nerves.

Antibody Formation↗