Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
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Cytokines are a heterogeneous group of polypeptide mediators of intercellular signalling required for an integrated response to a variety of external stimuli. Cytokines are extremely potent mediators that interact with specific high affinity receptors on the cell surface. The messenger ribonucleic acid (mRNA) of some of the cytokines e.g; Interferon-ß (IFN-ß), IFNg, GM-CSF and G-CSF have short half lives (<30 minutes) while the half lives of others e.g; IL-1ß, IL-2, IL-3, IL-4 and Tumour Necrosis Factor-a (TNFa) are upto 1-2 hours (Nicola, 1994). The expression and activity of cytokines are increased in conditions of tissue stress, phases of acute growth (as in embryogenesis and tissue repair), tissue dysregulation (e.g; chronic inflammatory states and tumour growth), infection and trauma (Hopkins and Rothwell, 1995; Giulian and Lachman, 1985). IL-1 induces fever (Blatteis, 1992), decreases appetite (Rothwell, 1991; McCarthy et al, 1985), alters the hypothalamic-pituitary axis (Gottschall et al, 1992; Dunn, 1990; Berkenbosch et al, 1992) and stimulates thermogenesis (Dascombe et al, 1989; Busbridge et al, 1989).

In literature, there have been certain discrepancies regarding IL-1 receptors and IL-1 expression in the brain, especially in hypothalamus (Farrar et al, 1987; Ban et al, 1991; Haour et al, 1990; Lechan et al, 1990). Despite the actions of IL-1 on thermogenesis and induction of fever, independent groups of investigators had not been able to show specific binding in hypothalamus. Secondly, those investigators who did show receptors for IL-1 in hypothalamus were able to identify these receptors in some, but not all, species, though the effects attributed to hypothalamus have been reported in many species. For example, Farrar and co-workers (1987) and Katsuura and co-workers (1988) report the presence of IL-1 receptors in the hypothalamic membranes of rat brain, but Haour and co-workers (1990) and Ban and co-workers (1991) report the presence of IL-1 receptors in the dentate gyrus of mouse brain but could not detect any IL-1 receptor binding sites in the rat brain. In contrast, Takao and co-workers (1990), using homogenate, described significantly higher binding of IL-1 in mouse brain compared to rat brain, but were also able to measure a low binding capacity in the rat brain. Thirdly, some investigators trying to replicate these experiments using similar experimental techniques, were unable to produce comparable results in terms of localisation of the receptors in brain areas of rat and mouse (see review by Rothwell, 1991). Similarly, IL-1 expression in hippocampus had been reported but the expression was reported to be around pyramidal cells in dendrites and axons (Lechan et al, 1990) whereas mRNA had been detected in the pyramidal cells (Jirikowski et al, 1990).

The main objectives of the experiments were (1) to observe the age-related changes in IL-1ß binding and expression in hippocampus and hypothalamus, (2) to compare the abilities of young and old mice to sustain a thermal challenge, and to observe any correlation between IL-1ß binding and IL-1ß expression in brains of these animals with their ability to sustain the thermal challenge, (3) to look at the effect of the cold challenge on IL-1ß binding and expression in hippocampus and hypothalamus and (4) to recognise the sites of IL-1ß expression in hippocampus.

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