EFFECT OF GAMMA-RADIATION ON BRUGIA L3 DEVELOPMENT IN-VIVO AND THE KINETICS OF GRANULOMATOUS INFLAMMATION-INDUCED BY THESE PARASITES

Previous studies have shown that the downregulation of parasite-specif ic cellular immune response in Brugia-infected jirds requires viable w orms but is not dependant on microfilariae (MF) for either induction o r maintenance of this phenomenon. To clarify further which life cycle stages induce filarial hyporesponsiveness, jirds were infected intrape ritoneally with third stage larvae (L3) exposed to 0, 15, 25, 35, 45, or 90 krad of gamma radiation to differentially alter L3 development. Necropsies were performed at 7, 14, 28, and 118 days postinoculation ( DPI). The degree of parasite development, intraperitoneal inflammation , and pulmonary granulomatous inflammation (PGRN) to parasite antigen- coated beads embolized in the lungs were monitored at the time of necr opsy. Parasite survival and worm lengths were inversely related to the irradiation dose. Gamma radiation at 35, 45, or 90 krad prevented lar val molt to the adult stage. Some parasites irradiated with 15 or 25 k rad developed beyond fourth stage larvae (L4) to infertile adult femal es. The PGRN peaked at 14 DPI in all infected groups. Downregulation o f the PGRN occurred after 14 DPI in groups that received nonirradiated L3 or L3 irradiated with 15 krad. No significant decrease of the PGRN occurred in groups that received parasites irradiated with more than 15 krad. Significant peritoneal inflammation as indicated by an increa se in macrophages occurred only in jirds that received nonirradiated L 3. These data demonstrate the importance of the adult stages in induci ng downmodulation in the absence of MF and suggest that the L4 may als o play a role in the induction of this phenomenon. An alternate conclu sion is that parasite burden and not developmental stage is important in the induction of this hyporesponsive state.