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Pharmacodynamic and Protective Properties of a Murine Lipopolysaccharide‐Specific Monoclonal Antibody in Experimental Pseudomonas aeruginosa Pneumonia in Mice
Author(s) -
Oishi Kazunori,
Sonoda Fuminari,
Miwa Hideaki,
Tanaka Hirofumi,
Watanabe Kiwao,
Matsumoto Keizo,
Pollack Matthew
Publication year - 1991
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.1991.tb01634.x
Subject(s) - pseudomonas aeruginosa , lipopolysaccharide , monoclonal antibody , biology , pneumonia , lung , microgram , microbiology and biotechnology , antibody , in vivo , immunology , pharmacology , monoclonal , medicine , in vitro , bacteria , biochemistry , genetics
We employed a Pseudomonas aeruginosa mouse pneumonia model to evaluate the ability of a murine monoclonal antibody (MAb) specific for the O‐side chain of P. aeruginosa Fisher Immunotype‐1 lipopolysaccharide (LPS) to achieve and sustain therapeutic levels in plasma and lung tissue, reduce bacterial populations in the lung, and prevent pneumonia‐associated mortality. An IgG3 MAb (Y1–5A4) administered to mice i.v. over a dose range of 125–1,000 μg/mouse produced plasma and lung tissue levels at 2 hr of 61–507 μg/ml and 4.3–150 μg/g, respectively. The 1,000 μg MAb dose reduced bacterial counts in lung tissue (logio cfu/g±S.D.) and blood (log 10 cfu/ml+S.D.) 20 hr post‐treatment (18 hr post‐challenge) from 10.00+ 0.66 to 7.66±0.91 (P<0.01) and from 4.39±0.81 to <3.0, respectively. Administration of MAb to mice in doses of 125–500 μg 2 hr prior to a 3 × 50% lethal bacterial challenge produced significant protection against death, with a calculated 50% protective dose of 167 μg. Protection was noted following administration of 1,000 μg of MAb up to 6 hr after bacterial challenge (P<0.05, compared with untreated control). Histological examination of lung tissue from infected mice revealed less acute inflammation, necrosis, and hemorrhage in MAb‐treated compared with untreated control animals and greater localization of Pseudomonas antigen within the phagocytic cells in alveolar space. These findings document the in vivo therapeutic efficacy of an LPS‐specific IgG MAb in a murine model of acute P. aeruginosa pneumonia, based in part upon the achievability of effective MAb concentrations in plasma and lung tissue.