Protection of mice from Mycobacterium avium infection by recombinant interleukin-12

Kobayashi, Keiko; Kasama, Tsuyoshi; Yamazaki, Junko; Hosaka, Michio; Katsura, Takashi; Mochizuki, Tomofumi; Soejima, Kazutaka; Nakamura, Reiko

doi:10.1128/aac.39.6.1369

Cited by 32 publications

(17 citation statements)

References 23 publications

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“…In contrast, blocking endogenous IL-12 activity or the simultaneous inhibition of both endogenous IL-18 and IL-12 activity decreased intrapulmonary levels of IFN-␥ by Ͼ90% and resulted in a persistent replicative L. pneumophila infection. In agreement with previous studies demonstrating a key role of IL-12 in immunity to other intracellular pathogens (11,12,18,23,34,36,41), these results suggest that IL-12 is the dominant cytokine in IFN-␥-mediated resolution of replicative L. pneumophila lung infection. Whether persistent replicative L. pneumophila lung infection in mice treated with anti-IL-12 MAb is due at least in part to IL-12-induced modulation of IL-18R expression, resulting in modulation of IL-18-mediated cell activation, is currently being investigated.…”

Section: Resultssupporting

confidence: 81%

Immunomodulatory Role of Endogenous Interleukin-18 in Gamma Interferon-Mediated Resolution of ReplicativeLegionella pneumophilaLung Infection

Brieland¹,

Jackson²,

Hurst³

et al. 2000

Infect Immun

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The in vivo role of endogenous interleukin-18 (IL-18) in modulating gamma interferon (IFN-␥)-mediated resolution of replicativeLegionella pneumophila, the causative agent of Legionnaires' disease, is an intracellular pathogen of host mononuclear phagocytic cells (MPCs), primarily alveolar macrophages (19,24,27). Resistance to primary replicative L. pneumophila lung infection is dependent on the induction of cellular immunity and is mediated in part by cytokines, including gamma interferon (IFN-␥) (8, 9). Growth of L. pneumophila within permissive MPCs requires iron. IFN-␥ limits MPC iron, creating an intracellular environment that is nonpermissive for L. pneumophila replication (8, 9). IFN-␥ in combination with other cytokines, including tumor necrosis factor alpha (TNF-␣), facilitates elimination of L. pneumophila from infected MPCs, likely through the induction of effector molecules, including nitric oxide (7).Interleukin-18 (IL-18) is a cytokine isolated from the livers of mice sequentially injected with heat-killed Propionibacterium acnes and lipopolysaccharide (28,29). Originally termed IFN-␥-inducing factor because of its ability to induce IFN-␥ in mice, IL-18 is now recognized to have pleotropic effects including (i) induction of proliferation of activated T cells; (ii) enhancement of the lytic activity of NK cells; (iii) induction of IFN-␥ and granulocyte-macrophage colony-stimulating factor production by activated T cells, B cells, and/or NK cells; and (iv) promotion of T helper type 1 (Th1) responses (20,22,25,29,39,40,44). Responsiveness to IL-18 is conferred by IL-18 binding to its cognate receptor, which consists of the IL-1 receptor (IL-1R)-related protein 1 chain (IL-1Rrp1) (also known as IL-1R5) and the IL-1R accessory protein-like chain (IL-1RAcPL) (also known as IL-1R7) (4, 38, 42; R. Debets, J. C. Timans, T. Churakowa, S. Zurawski, R. de Waal-Malefyt, K. W. Moore, J. S. Abrams, A. O'Garra, J. F. Bazan, and R. A. Kastelein, unpublished data). Recent studies have demonstrated that IL-18-mediated cell activation can be prevented by inhibiting IL-18 ligand receptor interaction, by administration of anti-IL18 antibody (28) or by administration of monoclonal antibodies which recognize either the IL-1R5 chain (42) of the IL-1R7 chain (Debets et al., unpublished data) or the IL-18R.Synergistic effects of IL-18 with other cytokines, including IL-12, have been described in vitro, including markedly increased IFN-␥ production by T cells in comparison to that induced by either cytokine alone (1,33,37,43). The molecular mechanism underlying the synergy between IL-18 and IL-12 may be explained in part by reciprocal modulation of cytokine receptor expression. Specifically, IL-18 has been demonstrated to upregulate IL-12R expression (42), while IL-12 has been shown to upregulate expression of the IL-18R (1, 43).IL-18 has been shown to play a key role in innate immunity to intracellular pathogens, including Mycobacterium tuberculosis (35) and Cryptococcus neoformans (32). However, the potential role of endogen...

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Section: Resultssupporting

confidence: 81%

Immunomodulatory Role of Endogenous Interleukin-18 in Gamma Interferon-Mediated Resolution of ReplicativeLegionella pneumophilaLung Infection

Brieland¹,

Jackson²,

Hurst³

et al. 2000

Infect Immun

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show abstract

“…Although IL-12 has been investigated most extensively in the treatment of cancer (37), a considerable body of literature supports IL-12 therapy for infectious disease as well. For example, systemic IL-12 has been shown to enhance host defense in animal models of infection with Listeria monocytogenes (55), Mycobacterium tuberculosis (13), Toxoplasma gondii (14), coxsackievirus (46), herpes simplex virus (28), bacteria (17), mycobacteria (26), cryptococcus (24), and Leishmania major (20). Local delivery of IL-12 has been used to treat experimental infections with Klebsiella pneumoniae (18) and Franciscella tularensis (12,44).…”

Section: Discussionmentioning

confidence: 99%

“…The link between IL-12 and IFN-␥ also stimulated our interest in IL-12 as a possible therapy for Pneumocystis infection. Treatment with IL-12 has been employed by other investigators to enhance immune responses to a variety of infectious pathogens (7,17,23,24,26,28), not including P. carinii.…”

mentioning

confidence: 99%

Interleukin-12 and Host Defense against MurinePneumocystisPneumonia

et al. 2008

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“…Oxygen radicals generated by NADPH oxidase and induction of nitric oxide (NO) by iNOS result in antimicrobial activity against many microorganisms (16,35). IL-12, TNF-␣, and IFN-␥ play important roles in the clearance of M. avium (2,13,26). Furthermore, macrophages produce IL-12, TNF-␣, and IFN-␣/␤ in response to ISS-ODN treatment (25,44).…”

Section: Iss-odn Protection In Vivo Is Not Mediated Through Augmentatmentioning

confidence: 99%

Enhancement of Innate Immunity againstMycobacterium aviumInfection by Immunostimulatory DNA Is Mediated by Indoleamine 2,3-Dioxygenase

Hayashi¹,

Rao²,

Takabayashi³

et al. 2001

Infect Immun

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Protection of mice from Mycobacterium avium infection by recombinant interleukin-12

Cited by 32 publications

References 23 publications

Immunomodulatory Role of Endogenous Interleukin-18 in Gamma Interferon-Mediated Resolution of ReplicativeLegionella pneumophilaLung Infection

Immunomodulatory Role of Endogenous Interleukin-18 in Gamma Interferon-Mediated Resolution of ReplicativeLegionella pneumophilaLung Infection

Interleukin-12 and Host Defense against MurinePneumocystisPneumonia

Enhancement of Innate Immunity againstMycobacterium aviumInfection by Immunostimulatory DNA Is Mediated by Indoleamine 2,3-Dioxygenase

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