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Tumour necrosis factor alpha antibody protects against lethal meningococcaemia
Author(s) -
Nassif X.,
Mathison J. C.,
Wolfson E.,
Koziol J. A.,
Ulevitch R. J.,
Son M.
Publication year - 1992
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.1992.tb01505.x
Subject(s) - biology , tumor necrosis factor alpha , neisseria meningitidis , antiserum , polyclonal antibodies , microbiology and biotechnology , bacteria , cytokine , antibody , immunology , necrosis , genetics
Summary Tumour necrosis factor alpha (TNF‐α) has been shown to be the principal mediator of Gram‐negative bacterial endotoxin‐induced shock. Nevertheless, evidence suggests that TNF‐α plays a beneficial role in controlling bacterial infections when multiplication of the microorganism is required to kill the host. Using an infant rat model of Neisseria meningitidis infection, we found that blood TNF‐α concentration reaches a peak three hours after intraperitoneal injection of 3 × 10 6 bacteria. Thereafter, the level of TNF‐α decreased and was undetectable six to eight hours after infection. A correlation was observed between the magnitude of initial TNF‐α response and a fatal outcome. Pretreatment of the animals with polyclonal anti‐TNF antiserum significantly reduced mortality relative to animals pretreated with control serum. However, pretreatment of animals with anti‐TNF antibody did not alter the bacterial invasion of the cere‐brospinal fluid. Injection of heat‐killed bacteria did not cause death and induced lower TNF‐α levels than the same number of live bacteria. This excludes the possibility that the role of TNF‐α is to mediate a shock induced by the endotoxin component of the bacterial inoculum. These results indicate that TNF‐α has a deleterious effect in this model of bacteraemia. Identification of the critical factors that determine the action of TNF‐α during lethal bacteraemia will lead to a better understanding of these diseases and the development of appropriate therapeutic intervention.