A Model for Screening Antagonists of the Immunosuppressive Response Induced by 5 Fluorouracil

A Model for Screening Antagonists of the Immunosuppressive

Response Induced by 5 Fluorouracil

We have developed an in vitro immunosuppression model based on the cell proliferation enhancing effects of the mitogens concanavalin A and lipopolysaccharide combined with the 5 fluorouracil (5 Fu) induced inhibitory effect on mouse spleen lymphocyte proliferation. The model was used to compare the antagonistic effects of different polysaccharide preparations on 5 Fu induced suppression of mouse spleen lymphocyte and mixed lymphocyte proliferation. Polysaccharide preparations F1 1 (from Gracilaria lemaneiformis) and BW (from Ganoderma lucidum) completely neutralized the mild inhibition of lymphocyte proliferation induced by 0.02 μg/mL 5 Fu. However,no positive corre lation was found between the stimulating effect of a given polysaccharide on lymphocyte proliferation and the antagonistic effect of that polysaccharide on 5 Fu induced suppression of lymphocyte proliferation. Thus,polysaccharide 19 (from G. lucidum) was most effective in stimulating lymphocyte proliferation but had no antagonistic effect on 5 Fu induced suppression of lymphocyte proliferation.

Immunosuppression; chemotherapeutic agent; polysaccharide

Cancer remains one of the most serious threats to human health,and tumor patho genesis and therapy continue to be the focus of much research[1]. Although chemotherapy is a highly effective therapy for killing tumors in clinical practice,there are associated adverse side effects including granulocytopenia,especially affecting neutrophils,and thrombocytopenia[2]. Furthermore,the immune system is often compromised and the patient may suffer from immunodeficiency[3]. Consequently,prolonged use of chemotherapeutic agents should be avoided but,since intermittently administered therapy is not as effective,there is a need to identify bioactive substances capable of reducing chemotherapy induced immuno suppression.

Previous research has showed that mushroom polysaccharides exhibit immuno regulatory and antitumor activities[4],and can also significantly moderate the immuno suppressive effects of chemotherapeutic agents[5]. However,fungal polysaccharides are highly diverse and often have complex structures and,in order to exploit these compounds more fully,an effective model for screening bioactivity needs to be developed. At present,screening for immunosuppressive compounds involves the use of animal models[6,7] but,while generally reliable,these systems are not appropriate for screening multiple samples due to time considerations and high material costs. Therefore,it would be preferable to undertake initial screening using an in vitro model followed by verification of any detected bioactivity using animal models. The antagonistic effect of Ganoderma lucidum polysaccharides on the immunosuppression of mixed mouse lymphocytes induced by ciclosporin,hydrocortisone,and anti tumor