Effect of Bacteriophage D29 on the Immune Function of Guinea Pigs with a Model of Tuberculosis

Objective To observe the effect of bacteriophage D29 on the humoral as well as cellular immune function of guinea pigs with a model of tuberculosis. Methods Guinea pig models of drug-sensitive and drugresistant tuberculosis were set up by using the method of subcutaneous challenge with the corresponding bacteria.The animals infected with drug-sensitive or drug-resistant bacteria were then randomly divided into the following groups respectively: the control group,bacterophage group,rifampin(RFP) group and combined chemotherapy group.Guinea pigs of the control group were given each 0.9% sodium chloride solution administered by gastrogavage q.o.d..Those of the RFP group were given each RFP solution containing 15(mg·kg~(-1)) of the drug administered by gastrogavage 3 times a week.Animals of the combined chemotherapy group were given each RFP+ethambutol+pyrazinamide+levofloxacin administered by gastrogavage q.o.d.,the doses of the 4 drugs being 15,25,25 and 6 mg·kg~(-1),respectively.Guinea pigs of the bacteriophage group were given each 1×10~(8) PFU(0.5 mL) of bacteriophage D29 administered by nasal dripping 3 times a week.The course of treatment in all 4 groups lasted 4-7 weeks.The dynamic changes in the serum titer of neutralizing antibodies against the bacteriophage in animals of the bacteriophage group,the changes in serum levels of IL-1,IL-4, IFN-γ in animals of all 4 groups 4 weeks after the beginning of the experiment were kept under observation.Phagocytosis of the bacteriophage by the macrophage was examined with electron microscopy. Results Neutralizing antibodies against the bacteriophage began to appear in the sera of the guinea pigs after they had been treated with the bacteriophage for 18 days and the titers of the antibodies were positively correlated with the time.Macrophages were shown to phagocytize and digest a portion of the bacteriophages as revealed by electron microscopy.The serum IL-2 contents in guinea pigs with the model of drug-sensitive tubercle bacilli infection were greater than those of the control animals after the former had been treated with RFP or the bacteriophage for 4 weeks.The serum IL-2 contents in guinea pigs with the drug-resistant tubercle bacilli infection were greater in those animals treated with RFP,bacteriophage and combined chemotherapy as compared with those in control animals.Among these,animals treated with the bacteriophage had the highest serum IL-2 content as compared with that of the controls(P0.05).Differences between the different groups of animals with respect to serum IL-4 and IFN-γ levels were insignificant. Conclusion The bacteriophage was shown to be provided with antigenic characteristics.It could stimulate the organism to produce neutralizing antibodies and promote the cellular immune function of the body so that the latter could act synergetically with the bacteriophage in the elimination of tubercle bacilli in the organism.