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344<br />

Yap and Ng<br />

after feedingwith lentinan but returned to baseline after 24 hr (Fig. 3a–d). The<br />

IL-1a (Fig. 3a) and IL-2 (Fig. 3b) peaked at 2 hr postfeeding with lentinan.<br />

Both the TNF-a and IFN-g peaked at 4 hr postfeeding(Fig. 3c and 3d).<br />

These results suggested that oral administration of lentinan may serve as<br />

a means of activatingthe immune system, provokingthe immune responses<br />

required for disease prevention. Lentinan, once ingested, may encounter the<br />

gut-associated lymphoid tissue (GALT), which is a well-developed immune<br />

network, evolved to protect the host from infectingpathogens. Lentinan may<br />

also be absorbed into the systemic circulation, thereafter, involved in inducing<br />

immune systems against future pathogenic attack. Quantitative analysis of<br />

orally administered lentinan in murine blood carried out usinglimulus<br />

colorimetric test demonstrated that pure lentinan was detected in the murine<br />

blood and peaked at 0.2 mg(equivalent to the usual intravenous or intraperitoneal<br />

inoculation dosage) 30 min after feeding (Yap and Ng, unpublished<br />

data).<br />

When fed with c<strong>ru</strong>de mushroom homogenates, IL-1a, IL-2, and TNF-a<br />

levels were also induced but to much lower levels when compared to lentinanfed<br />

cohort. The IFN-g level was not significantly induced. The lipid and<br />

protein fractions from the mushrooms did not result in noticeable induction<br />

of any of the four cytokines tested and was at the baseline like the buffer-fed<br />

cohort (control).<br />

Many interestingbiological activities of lentinan have been reported.<br />

This included an increase in the activation of nonspecific inflammatory<br />

responses such as APP (acute-phase protein) production (87), vascular<br />

dilation, and hemorrhagic necrosis of the tumors (88). Bradykinin-induced<br />

skin reaction could be used as an index of vascular reactions against lentinan<br />

and this skin reaction could be used to moniter the host sensitivity to lentinan<br />

in antitumor responses (89).<br />

Activation and generation of helper and cytotoxic T cells (10,67,79,90–<br />

93) is an essential aspect of lentinan treatment. The augmentation of immune<br />

mediators such as IL-1 and IL-3, colony-stimulatingfactor(s) (94), migration<br />

inhibitory factor (32,94,95), and increasingthe capacity of PBM (peripheral<br />

blood mononuclear) cells (52,53) contributed additively to the antitumor<br />

efficacy. Wangand Lin (96) postulated that the immunomodulatingeffect of<br />

lentinan might be relevant to change of T-cell subpopulation and increase of<br />

TNF production.<br />

The recent study of Yap and Ngconfirmed that T-lymphocytes were<br />

increased significantly (fourfold, p < 0.001, Student’s t-test) after feeding<br />

with lentinan (Table 2). The CD3, CD4 (T-helper), and CD8 (T-cytotoxic)<br />

lymphocytes were isolated usingT-cell-enrichment columns. All three types<br />

of CD lymphocytes were activated in comparison with the buffer-fed controls.<br />

It was noted that the placebo (controls) effects did result in some degree of

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