The differential effect of Eriobotrya japonica hydrophilic extract on cytokines production and modulation

Stimulating or modulating the release of cytokines by immunomodulators or immunostimulating agents is an attractive mode for treating several diseases such as viral infections. For instance, patients with viral infections are in need of increasing or inducing T helper 1 (Th1) or proinflammatory cytokines, which ultimately activate T cytotoxic and Natural killer lymphocytes to kill virally infected cells. Of these agents, we found that the water extract (hydrophilic extract) from the leaves of Eriobotrya japonica (EJHE) can induce and modulate cytokines in a dose-dependent manner. Twenty-four hour exposure of increasing concentrations of EJHE enhanced significantly (p<0.001) the production of IL-12 p70, IFN-γ and TNF-α from PHA+LPS-stimulated whole blood. However, the production of IL-12 p70, IFN-γ and TNF-α was reduced at high EJHE concentrations (10–100µg/ml). No significant changes in the production of IL-10 were seen. In addition, EJHE reversed significantly the inhibitory effect of hydrocortisone on the cytokines production from PHAS+LPS stimulated whole blood. Without PHA and LPS, EJHE was found to induce IFN-γ, IL-12 p70, TNF-α, and IL-10 from whole blood culture in a concentration dependent manner. The maximum induction of IFN-γ, IL-12 p70, and TNF-α by EJHE was between 1–10µg/ml. On the other hand, IL-10 induction kept increasing even at the highest concentration used 100µg/ml of EJHE. Furthermore, intra-peritoneal injection of EJHE into mice increased significantly serum cytokines level mainly at 1 and 100µg/ml. Two-hour post i.p. injection, EJHE increased serum IFN-γ, TNF-α, and IL-10 to ˜750, 1000, and 250 pg/ml, respectively. However, 24h post i.p. injection, the levels of TNF-α, and IL-10 were similar to basal levels but IFN-γ levels were 200 pg/ml. These results indicate that EJHE induces proinflammatory and Th1 cytokines in a concentration dependent manner and the effect of this induction should be studied further in viral models to check the efficacy of such cytokine induction.