A polyvalent human gamma-globulin immune to Pseudomonas aeruginosa: passive protection of mice against lethal infection.

As a means to development of guidelines for therapeutic application to human disease, preparations of human polyvalent gamma-globulin immune to Pseudomonas aeruginosa (PG) were studied in acute infections in mice. PG was highly effective in controlling lethal infections induced in mice by the major immunotypes of P. aeruginosa; greater than or equal to 10 microgram of of gamma-globulin per mouse protected against challenge with less than or equal to 10(6) 50% lethal doses of P. aeruginosa. PG was less than or equal to 57 times more effective than normal human gamma-globulin. The active antibody component is specific for each immunotype; it is of the IgG type and undoubltedly is directed against the O-antigen. PG was was not protective against challenge with Escherichia coli, Enterobacter cloacae, Proteus mirabilis, or Klebsiella pneumoniae; a low degree of cross-protection was seen against Serratia marcescens. In a model infection involving mice in a terminal stage of advanced P. aeruginosa infection, human plasma immune to P. aeruginosa proved ineffective, but the gamma-globulin component showed moderate activity. The apparent irreversibility of this late-stage infection is not clearly ascribable to a toxin. It is postulated that the successful treatment of advanced P. aeruginosa infections in humans would require multiple therapeutic approaches, including passive immunization with a high-potency, specifically immune globulin.