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Infect. Immun., Jun 1995, 2262-2268, Vol 63, No. 6
SA Dalrymple, LA Lucian, R Slattery, T McNeil, DM Aud, S Fuchino, F Lee and R Murray
We have produced interleukin-6 (IL-6)-deficient mice to examine, in vivo,
the wide variety of biological activities attributed to this
multifunctional cytokine. To investigate the role of IL-6 during infectious
disease, IL-6-deficient mice were challenged with sublethal doses of
Listeria monocytogenes, a facultative intracellular bacterium. While normal
control animals were able to clear the infection, mutant animals exhibited
a high mortality rate and showed uncontrolled replication of the bacteria
in the spleen and liver at 2 and 3 days postinfection. Sections of infected
tissues showed an increase in the number and severity of inflammatory foci.
All aspects of this phenotype in the mutant animals were completely
reverted upon administration of recombinant murine IL-6 (rIL-6). Various
parameters of natural killer (NK) cell and macrophage function were
unaffected in the challenge of the mutant animals. However, IL-6-deficient
animals failed to mount peripheral blood neutrophilia in response to
listeriosis, whereas control animals displayed a prominent neutrophilia in
the blood at 24 and 48 h postinfection. Additionally, we analyzed the
efficacy of rIL-6 in protecting animals devoid of lymphocytes or devoid of
neutrophils during listeriosis. Administration of rIL-6 was protective to
animals devoid of lymphocytes, suggesting that the rIL-6 protective effect
was not mediated through lymphocytes. In contrast, control and mutant
animals depleted of neutrophils were refractory to the rIL-6 protective
effect. These data suggest that IL-6 is critical early during listeriosis,
perhaps acting by stimulating neutrophils either directly or indirectly.
Additionally, these data show a promising therapeutic potential for rIL-6
administration during opportunistic infection.
Copyright © 1995, American Society for Microbiology
Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia
Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304, USA.
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