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Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia.
Infect Immun. 1995 Jun; 63(6):2262-8.II

Abstract

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.

Authors+Show Affiliations

Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7768607

Citation

Dalrymple, S A., et al. "Interleukin-6-deficient Mice Are Highly Susceptible to Listeria Monocytogenes Infection: Correlation With Inefficient Neutrophilia." Infection and Immunity, vol. 63, no. 6, 1995, pp. 2262-8.
Dalrymple SA, Lucian LA, Slattery R, et al. Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia. Infect Immun. 1995;63(6):2262-8.
Dalrymple, S. A., Lucian, L. A., Slattery, R., McNeil, T., Aud, D. M., Fuchino, S., Lee, F., & Murray, R. (1995). Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia. Infection and Immunity, 63(6), 2262-8.
Dalrymple SA, et al. Interleukin-6-deficient Mice Are Highly Susceptible to Listeria Monocytogenes Infection: Correlation With Inefficient Neutrophilia. Infect Immun. 1995;63(6):2262-8. PubMed PMID: 7768607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia. AU - Dalrymple,S A, AU - Lucian,L A, AU - Slattery,R, AU - McNeil,T, AU - Aud,D M, AU - Fuchino,S, AU - Lee,F, AU - Murray,R, PY - 1995/6/1/pubmed PY - 1995/6/1/medline PY - 1995/6/1/entrez SP - 2262 EP - 8 JF - Infection and immunity JO - Infect. Immun. VL - 63 IS - 6 N2 - 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. SN - 0019-9567 UR - https://www.unboundmedicine.com/medline/citation/7768607/Interleukin_6_deficient_mice_are_highly_susceptible_to_Listeria_monocytogenes_infection:_correlation_with_inefficient_neutrophilia_ L2 - http://iai.asm.org/cgi/pmidlookup?view=long&pmid=7768607 DB - PRIME DP - Unbound Medicine ER -