The differential effect of Eriobotrya japonica hydrophilic leaf 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 may be 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 Eriobotrya japonica hydrophilic leaf extract (EJHE) can induce and modulate cytokines in dose-dependent manner. Twenty-four hour exposure of increasing concentrations of EJHE increased significantly (p<0.001) the production of IFN-gamma and TNF-alpha, from PHA+LPS-stimulated whole blood. However, the production of IFN-gamma and TNF-alpha plateaued at high EJHE concentrations (10-100 microg/ml). No significant changes in the production of IL-10 were seen. In addition, EJHE at 1 and 10 microg/ml reversed significantly (p < 0.01) the inhibitory effect of hydrocortisone on the IL-12 p70, IFN-gamma and TNF-alpha production from PHAS+LPS stimulated whole blood. Without PHA and LPS, EJHE was found to induce significantly (p<0.001) IFN-gamma, IL-12 p70, TNF-alpha, and IL-10 from whole blood culture in concentration dependent manner. The maximum induction of IFN-gamma, IL-12 p70, and TNF-alpha by EJHE was at 1 and 10 microg/ml. On the other hand, IL-10 induction kept increasing even at the highest concentration used (100 microg/ml) of EJHE. Furthermore, intra-peritoneal injection of EJHE into mice increased significantly serum cytokines level mainly at 10 and 100 microg/ml. Two-hour post i.p. injection, EJHE increased serum IFN-gamma, TNF-alpha, and IL-10 to approximately 750, 1000, and 250 pg/ml, respectively. However, 24h post i.p. injection, the levels of TNF-alpha, and IL-10 were similar to basal levels but IFN-gamma levels were 200 pg/ml. These results indicate that EJHE induces proinflammatory and Th1 cytokines in concentration dependent manner and the effect of this induction should be studied further in viral models to check the efficacy of such cytokine induction.