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Infect. Immun., May 1997, 1800-1807, Vol 65, No. 5
AC Savoy, DM Lupan, PB Manalo, JS Roberts, AM Schlageter, LC Weinhold and TR Kozel
Passive immunization with monoclonal antibodies (MAbs) specific for the
major capsular polysaccharide of Cryptococcus neoformans alters the course
of murine cryptococcosis. During studies of passive immunization for
treatment of murine cryptococcosis, we noted the occurrence of an acute,
lethal toxicity. Toxicity was characterized by scratching, lethargy,
respiratory distress, collapse, and death within 20 to 60 min after
injection of antibody. The toxic effect was observed only in mice with a
cryptococcal infection and was reduced or absent in the early and late
stages of disease. The clinical course and histopathology were consistent
with those for shock. There was considerable variation between mouse
strains in susceptibility to toxicity. Swiss Webster mice from the Charles
River colony were most susceptible, followed by C3H/He, BALB/c, and C57BL/6
mice. DBA/2 mice and Swiss Webster mice from the Simonsen colony were
resistant. Acute toxicity was mimicked by injection of preformed complexes
of MAb and purified polysaccharide. The toxic effect was also produced by
injection of MAbs into mice that were preloaded with polysaccharide. The
toxic effect was not blocked by treatment of mice with chloropheniramine or
anti-tumor necrosis factor alpha antibodies or by depletion of complement
components via pretreatment with cobra venom factor. Toxicity was reduced
by treatment of mice with high doses of epinephrine, dexamethasone, or
chlorpromazine. Finally, the toxic effect was completely blocked by
treatment of mice with the platelet-activating factor antagonist WEB 2170
BS or by pretreatment of mice with the liposome-encapsulated drug
dichloromethylene diphosphonate, a procedure which depletes macrophages
from the spleen and liver.
Copyright © 1997, American Society for Microbiology
Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis
Department of Microbiology, University of Nevada, Reno 89557, USA.
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