IL-12 Production Induced by Agaricus blazei Fraction H (ABH) Involves Toll-like Receptor (TLR)

Agaricus blazei Murill is an edible fungus used in traditional medicine, which has various well-documented medicinal properties. In the present study, we investigated the effects of hemicellulase-derived mycelia extract (Agaricus blazei fraction H: ABH) on the immune system. First, we examined the cytokine-inducing activity of ABH on human peripheral mononuclear cells (PBMC). The results indicated that ABH induced expression of IL-12, a cytokine known to be a critical regulator of cellular immune responses. Flow cytometric analysis demonstrated the induction of IL-12 production by the CD14-positive cell population, consisting of monocytes/macrophages (Mo/Mφ). Furthermore, the elimination of Mo/Mφ attenuated IL-12 production in PBMC. ABH-induced IL-12 production was inhibited by anti-CD14 and anti-TLR4 antibodies but not by anti-TLR2 antibody. The activity of ABH was not inhibited by polymyxin B, while the activity of lipopolysaccharide used as a reference was inhibited. Oral administration of ABH enhanced natural killer (NK) activity in the spleen. These findings suggest that ABH activated Mo/Mφ in a manner dependent on CD14/TLR4 and NK activity

Morbidity and nutritional impairment in relation to CD4 count in a Zambian population with high HIV prevalence

The HIV epidemic has greatly increased morbidity in many African cities and severe undernutrition is a prominent feature of the clinical presentation. However, there is little information about the relationship of morbidity or nutritional status to immune damage at a population level. We report a cross-sectional study of morbidity and nutritional status in relation to CD4 count in an impoverished urban community in Lusaka, Zambia, at enrollment into a longitudinal study. Over a 2 month period in 1999, 261 (52%) of 506 adults resident in one area were interviewed and examined. Of 186 adults who consented to testing, 33 (51%) of 65 who were HIV seropositive reported symptoms of disease compared to 39 (32%) of 121 who were HIV seronegative (OR 2.2, 95%CI 1.1-4.2; P=0.02). Peripheral blood CD4 counts in HIV seronegative individuals were broadly similar to norms in developed countries, but 8 (7%) had CD4 counts below 500 cells/microl. Morbidity in HIV seropositive adults was dominated by tuberculosis (n=11), other respiratory infections (5) or persistent diarrhoea (4), and affected individuals had a wide range of CD4 counts. Nutritional impairment was evident in HIV seropositive adults with clinical evidence of opportunistic infection (OI), not those with asymptomatic HIV infection. Unexpectedly, we also noted that systolic blood pressure was reduced progressively in HIV infection and in those with OI. In conclusion, HIV-related morbidity was dominated by a small number of treatable infectious diseases occurring over a wide range of CD4 count. Nutritional impairment was associated with OI