Pyrogallol: A novel tool for screening immunomodulators

Objective: To induce immunosuppression in rats by pyrogallol and to develop a novel model to screen the immunomodulatory activity of a known agent. Material and Methods: In order to induce immunosuppression, pyrogallol was daily administered to rats for 7 days in different doses (10, 25, 50 and 100 mg/kg, i.p.). On Day 7 and 13, the rats were sensitized with sheep red blood cells (SRBC) to assess the humoral immune response. On Day 20, SRBC were injected in the subplantar region of the hind paw, and an increase in the paw volume was recorded on Day 22 to assess the cell-mediated immune responses. The phagocytosis in the peritoneal macrophages was assessed on the last day. The parameters of oxidative stress such as lipid peroxidation (LPO), reduced glutathione (GSH) content, superoxide dismutase (SOD) and catalase (CAT) activities were assessed on the last day. In another set of experiment, the immunomodulatory activity of Rubia cordifolia (RC) (50, 100, and 200 mg/kg, p.o., daily from Day 1 to Day 22) was screened in rats in whom immunosuppression was induced by a minimum effective dose of pyrogallol (50 mg/kg). Results: The dose of 25 mg/kg of pyrogallol suppressed only the humoral immunity (P<0.05), while 50 and 100 mg/kg dose significantly (P<0.01) impaired all the parameters i.e. humoral immunity, cell-mediated immunity and phagocytosis (P<0.01). It also caused a dose-dependent increase in the LPO levels, depletion of GSH, and decrease in activities of SOD and CAT. The treatment with the alcoholic extract of Rubia cordifolia significantly prevented the influence of the minimum effective dose of pyrogallol (50 mg/kg) on all immunological parameters and concurrently prevented the changes in the marker parameters of oxidative stress. The dose of 100 mg/kg was found to be optimum for this purpose. Conclusion: Fifty mg/kg (i.p., daily for 7 days) appears to be the minimum dose of pyrogallol, which can induce significant immunosuppression in rats. The correlation analysis indicated that pyrogallol-induced immunosuppression is related to oxidative stress. In addition, it was found that the immunomodulatory activity of a known agent could be successfully screened by this method. Thus, pyrogallol can be used as an experimental tool to induce immunosuppression while screening the immunomodulatory activity of any agent.