Prophylactic and therapeutic use of an anti-brevetoxin (PbTx-2) antibody in conscious rats.

A polyclonal antiserum was investigated for prophylactic and therapeutic use in the treatment of brevetoxin intoxication. Conscious, tethered male rats were pre-treated with 1 ml of anti-brevetoxin IgG (PbAb) or control IgG by a 10 min infusion, then given brevetoxin (25 micrograms/kg) by a 1 hr infusion. Rats pre-treated with control IgG demonstrated signs of brevetoxin intoxication; these signs were absent in rats pre-treated with PbAb. In therapy studies, rats were infused for 1 hr with 100 micrograms/kg brevetoxin, followed immediately by 2 ml of either PbAb or control IgG. During toxin infusion, both groups showed signs of brevetoxin intoxication. Rats treated with control antibody died within 6 hr. In rats treated with PbAb, respiratory rates began to return toward baseline almost immediately, and fewer neurological signs developed. After 24 hr, nearly all neurological signs had disappeared and both core and peripheral temperatures had returned to normal. There was a time differential between two groups of signs, suggesting high and low accessibility compartments for the antibody. These compartments probably represent central and peripheral nervous system. All animals treated with PbAb survived at least 8 days. These results suggest that PbAb has both therapeutic and prophylactic potential in the treatment of brevetoxin intoxication. Further, because of the differential in efficacy in reversing central and peripheral nervous system signs of brevetoxin intoxication, it provides useful new information on the mechanism of action of this toxin.