Increased glia reactivity is accompanied by elevated IL-1β [44] and [46]. Because broccoli diet decreased markers of glial reactivity in aged mice, we examined IL-1β expression to determine whether broccoli diet attenuated additional inflammatory mediators. Interleukin-1β is a key inflammatory cytokine in both the peripheral and central immune response [47]. Interleukin-1β
induces sickness behaviors such as anorexia, decreased locomotion, and social activity when exogenously administered, whereas inhibition of IL-1β signaling attenuates sickness behaviors in response to LPS treatment [30], [48] and [49]. For these reasons, we hypothesized HSP inhibitor that broccoli diet would exert an anti-inflammatory benefit by inhibiting IL-1β expression, and this would attenuate LPS-induced sickness behaviors. In this study, decreased social behavior was paralleled by increased IL-1β in brain, but there was no evidence that broccoli diet moderated LPS-induced sickness behavior. It is possible that the dose of LPS used (0.33 mg/kg) overwhelmed the anti-inflammatory dietary effects of consuming broccoli. It is also likely that the anorexic effect of LPS-induced sickness limited broccoli intake, resulting
in lowered SFN exposure. Indeed, we observed that 24-hour food consumption was decreased in LPS-treated mice compared to saline controls (data not shown). Sulforaphane is metabolized and excreted rapidly after broccoli consumption, and metabolites are not retained in tissue http://www.selleckchem.com/products/INCB18424.html past 24 hours [50], [51] and [52]. It seems plausible that diminished intake
of broccoli during the 24-hour sickness period could account for the lack of effectiveness against acute peripheral inflammation. Our findings are in contrast to other studies where dietary luteolin, resveratrol, or α-tocopherol and selenium improved LPS-induced sickness behavior in aged mice. Collectively these nutritional interventions suggest that dietary supplements are a viable therapeutic vehicle to ameliorate prolonged sickness in aged models [31], [53] and [54]. A more Mannose-binding protein-associated serine protease successful approach may be to incorporate SFN in supplement form into the diet. In agreement with this approach, some studies have demonstrated reduced neuroinflammation using purified SFN given intraperitoneally at doses of 50 mg/kg, which is several-fold higher than could be reasonably obtained through the 10% broccoli diet [36] and [41]. It remains to be determined whether the concentrations of SFN that were necessary to achieve reductions in inflammatory markers in these studies can be obtained through voluntary dietary consumption. Broccoli was selected for this study because it is a frequently consumed glucoraphanin-containing vegetable [55] and [56].