Prevention of immune complex disease (Serum Sickness) by antagonists of vasoactive amines

Abstract

Antagonists of vasocative amines prevent localization of circulating immune complexes in rabbits, thereby preventing acute or chronic serum sickness (S.S.) and causing amelioration of chronic complex-induced glomerulonephritis. The opportunity to apply these observations to the human has been afforded by a recent epidemic of diphtheria. We have studied 119 hospitalized individuals who each received 20–100,000 u of equine diphtheria antitoxin. Every patient was randomly selected to receive either placebo or one of two antagonists of histamine and serotonin, cyproheptadine (Periactin) or hydroxyzine HCI (Atarax). The oral medications were taken from the 4th through 16th day after antitoxin, in doses adequate to maintain continuous therapeutic blood levels of drug.Data on 100 cases are complete. None of 15 placebo or 27 drug-treated children under age 10 had S.S. Six of 23 (26.1%) older placebo-treated patients developed S.S., lasting 2–5 days. Of the 29 Periactin and 6 Atarax patients over age 9, only 2 (5.7%) manifested definite S.S. Serum hemolytic complement activity was lowered in most of the cases with S.S., but was low in many individuals without S.S. in the second week after antitoxin. Studies of horse globulin elimination and serum immune complexes should clarify the pathogenetic mechanisms. These preliminary findings suggest that S.S. in humans can be prevented by antagonists of permeability factors required for the passive deposition of circulating immune complexes, and that this approach deserves evaluation in the management of chronic immune complex diseases.