INDUCTION AND PREVENTION OF SHOCK-LIKE LETHAL SIDE-EFFECTS AFTER MICROFILARICIDAL TREATMENT IN FILARIAE INFECTED RODENTS

In contrast to human carriers of microfilariae, filariae infected rode nts generally tolerate an effective microfilaricidal treatment without obvious signs of adverse reactions. The study shows, however, that al so the filariae (Litomosoides carinii, Brugia malayi) infected rodent Mastomys coucha can be rendered sensitive to side effects of the treat ment by the administration of D-galactosamine (D-Gal), due to reductio n of liver UTP levels. Independent of the drug (diethylcarbamazine, iv ermectin, CGP 20376) and the parasite species, D-Gal-primed infected a nimals died within 4 days after a microfilaricidal treatment. Lethal e ffects did also occur in naive animals to which microfilariae had been transfused 18 h prior to the challenge with D-Gal and a microfilarici dal, provided the animals had received at least approximately 10(3) la rvae/g body weight. Both infected animals and naive recipients of micr ofilariae could be protected from death by cyclosporin A, polyclonal a ntibodies to mouse TNF or suitable amounts of NG-monomethyl-L-arginine . Pentoxifylline was less protective. The results suggest that compone nts play a role in adverse reactions after microfilaricidal treatment, which are released by dying/dead microfilariae and may interact with T lymphocytes independent of a specific state of immunity. In a sequel a, TNF released by T cells seems to induce an excess synthesis of N-ox ides which appear to be the final morbific agent.