Induction and prevention of shock-like lethal side effects after microfilaricidal treatment in filariae infected rodents.

Abstract

In contrast to human carriers of microfilariae, filariae infected rodents generally tolerate an effective microfilaricidal treatment without obvious signs of adverse reactions. The study shows, however, that also the filariae (Litomosoides carinii, Brugia malayi) infected rodent Mastomys coucha can be rendered sensitive to side effects of the treatment by the administration of D-galactosamine (D-Gal), due to reduction of liver UTP levels. Independent of the drug (diethylcarbamazine, ivermectin, CGP 20376) and the parasite species, D-Gal-primed infected animals died within 4 days after a microfilaricidal treatment. Lethal effects did also occur in naive animals to which microfilariae had been transfused 18 h prior to the challenge with D-Gal and a microfilaricidal, provided the animals had received at least approximately 10(3) larvae/g body weight. Both infected animals and naive recipients of microfilariae could be protected from death by cyclosporin A, polyclonal antibodies to mouse TNF or suitable amounts of NG-monomethyl-L-arginine. Pentoxifylline was less protective. The results suggest that components 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 sequela, TNF released by T cells seems to induce an excess synthesis of N-oxides which appear to be the final morbific agent.