*Corresponding author e-mail: lcasiraghi@unq. edu. ar Introduction: Diverse lines of research have linked the circadian system to immune function, from daily regulation of immune cells to the effect of immune challenges on the output of circadian rhythms. This bidirectional interaction between both systems has gone under intensive study in recent years and is proving to be an interesting field of clinical research, Moreover, it is becoming increasingly important as circadian disturbances are being related to cancer processes, as risk factors or even as prognosis markers. According to previous research from our lab and other reports, the circadian rhythm of activity can be affected by immune acute or chronic stimuli, which can act directly on the SCN in mammals. In this direction, we have performed several experiments to assess what kind of molecules can result in circadian and whether these effects are SCN mediated and how. Results: We had previously reported that LPS injection at CT15 induce photic-like phase delays in wheel-running rhythms, and we now show that such responses are partially inhibited in TLR4 (toll-like receptor 4) null mice. Also, LPS- induced reduction of activity (masking) is impaired in mutant mice. LPS effects appear to be mediated by central proinflammatory cytokine activity. Reduction of activity has also been reported in hamsters after chronic infusion of TGF-α via an osmotic pump. We tried to reproduce these results in mice, and we obtained a severe fall in daily activity in both control and treated groups, but with a stronger effect in TGF-α treated animals. However, we found no significant changes in per-luc expression in SCN transgenic slices when treating with TGF- or other cytokines. Since we have previously reported that SCN glia is a immune-circadian interface, we also analyzed SCN transfected astrocytes in culture and found a significant reduction of perl-luc expression after TNF-α treatment. Conclusion: Here we show that endotoxin and cytokine-mediated circadian effects are the result of a complex network of pathways which in some cases affect clock gene expression and might be relevant for specific patophysiological mechanisms. Publication History Article published online: 16 June 2026 © 2009. Brazilian Sleep Academy. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https: //creativecommons. org/licenses/by-nc-nd/4. 0/) Thieme Revinter Publicações Ltda. Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil
Casiraghi et al. (2009) studied this question.