Studies on the mechanism of action of 5-Fluorouracil : efffect on Interleukins - IL-1, IL-2, IL-4 and IL-6

Abstract

5-Fluorouracil is a potent anticancer agent which is clinically used against a large number of tumors namely colorectal cancer, breast cancer, liver cancer etc. Prolonged treatment with the drug is required to achieve success in chemotherapy. Early work on the effect of FUra suggested, possible adverse effect on the host immune system. Subsequently, it has been shown that several cytokine patterns are altered during cancer chemotherapy. Since immunosuppression is not desirable during cancer chemotherapy and since not enough information is available on the effect of FUra on key cytokines, this work was undertaken to fill the lacunae existing in our knowledge on the effect of this drug on cytokine balance, specifically on key cytokines like IL-1, IL-2, IL-4 and IL-6. The mechanisms by which the changes in cytokine balance is altered is also investigated. Cytokines and growth factors contain an octanucleotide sequences rich in uracil residues at the 3' untranslated regions of their genes. FUra exerts its biological effect by inhibiting thymidylate synthetase as well as getting incorporated into various species of RNA as well as DNA. This RNA mediated mechanism of action makes cytokines with the uracil rich octanucleotide sequences as prime target for FUra action. Thus effect of FUra has been examined on these cytokines. In summary since the immunomodulatory role of FUra is bound to affect the results of chemotherapy, investigations and understanding the nature of immunomodulation by FUra is required. Thus the present work has been undertaken to study the effect of FUra on various cytokines and their receptors in order to throw light on the mechanism of immunomodulation on the FUra treatment.