Int. J. Environ. Res. Public Health 2010, 7 955 whose activity in turn depends on binding with CRY, and correspondingly the magnetic field-dependent function of Cryptochrome (see Figure 6). Interestingly, the transcription complex CLOCK/BMAL1 also regulates the transcriptional activity of the glucocorticoid receptor [102]. Furthermore, it is known that the relative abundance of CBP in the nucleus can influence NF-kB and glucocorticoid receptor transcriptional antagonism [103]. At the same time, CBP binds BMAL1 very closely to the CRY binding cite. Thus, we can hypothesize that magnetic fields can influence the duration of the CBP-BMAL1 interaction via regulation of the functional activity of CRY. In turn, prolonged CBP retention by the CLOCK/BMAL1 transcription complex may influence the equilibrium between pro-inflammatory and immune-suppressive signals in cells and tissues. Together, the data suggest that the major circadian complex indirectly influences the functions of every organ and tissue inside the body through modulation of both: the NF-κB- and glucocorticoids-dependent signaling pathways. Another way magnetic field regulation of the NF-κB target genes provides participation of the magnetic field-sensitive CRY in mechanism of active transcriptional repression is implemented by CLOCK/BMAL1/CRY complex [60] (see chapter 4.2). For example, induction of NF-κB target genes in response to stress can occur only under those conditions (time of the day and magnetic field parameters) when CLOCK/BMAL1 is functioning as an activator and does not block the activity of other transcription factors. And vice versa, when the CLOCK/BMAL1/CRY complex acts as an active transcriptional repressor, the induction of NF-κB target genes and other stress-induced genes will be attenuated or completely suppressed. Therefore, the pattern of stress-induced gene expression and an organism’s response to stress will depend on the functional activity of CRY, which in turn can be regulated by magnetic fields. This mechanism allows external magnetic fields to produce global regulatory effects on gene expression. Indeed, the ability of electromagnetic fields to affect non-circadian gene regulation has been confirmed in numerous reports [18,28,60,104-106], reviewed in [29,77]. Definite immunological alterations caused by EMF exposure have been described (reviewed in [107]). A significant decrease in leukocyte, erythrocyte, lymphocyte and monocyte counts in mice chronically exposed to weak EMF was detected [108]. The intensity of EMF in these experiments was 5.0 microT, several times weaker than the geomagnetic field strength. In human populations, chronic exposure to weak ELF EMF (50 Hz, 0.2-6 microT) resulted in a significant fall in total lymphocytes and the T-helper subpopulation, whereas there was an increase in NK cells. Among other manifestations of the EMF exposure, there was an increase in the degree of neurovegetative disorders (i.e., physical fatigue, psychical asthenia, depressive tendency, irritability) [109]. Significant elevation of phagocytic activity, stimulation of free radical release and IL-1b production were detected in macrophages exposed to an ELF magnetic field [110].