INDUCTION OF DEPRESSION BY EXPOSURE TO DAMP ...

esulting in the activation on NF-κβ for the production of inflammatory cytokines (Hohl
et al., 2005; Underhill et al., 1999; Ozinsky et al., 2000). Other receptors have also been
identified that recognize β-glucans, including the C-type lectin receptor called dectin-1
(Steele et al., 2005), CR3 (Brown, 2006), lactosylceramide (Zimmerman et al., 1998),
and scavenger receptors (Brown, 2006).
Many studies have shown cytokine release by immune cells exposed to non-
purified β-glucan, which includes other membrane antigens (Olsson and Sundler, 2007).
Some studies suggest that the binding of β-glucans alone does not induce the release of
inflammatory cytokines (Li et al., 2007), but that they act only in an adjuvant capacity by
potentiating the effects of other agents (Williams, 1987). However, some studies have
shown that purified β-glucan can induce significant inflammatory reactions (Young et al.,
2003). These apparent conflicting findings are likely due to differences in physical
characteristics of the β-glucan used, such as size, complexity, and solubility. These
variations appear to affect their immunostimulatory properties by modulating their ability
to bind to receptors that recognize β-glucan (Bohn and BeMiller, 1995; Young et al.,
2003; Okazaki et al., 1995). In general, studies indicate that particulate glucans induce
more potent inflammatory responses than soluble glucans (Young et al., 2003), and large
particles are more inflammagenic than small particles (Suzuki et al., 1992).
Significant differences between soluble and particulate forms of β-glucans have
been realized. Particulate β-glucan from multiple fungal sources has been shown to
stimulate production of proinflammatory cytokines (Ishibashi et al., 2001), lower the
CD4 + /CD8 + ratio (Young et al., 2006; Kimura et al., 2007) and shift the immune reaction
to Th1 dominance as demonstrated by increased IFN-γ/IL-4 production ratio (Kimura et
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