Impaired immune and acute-phase responses in interleukin-6-deficient mice

  title={Impaired immune and acute-phase responses in interleukin-6-deficient mice},
  author={Manfred Kopf and Heinz Baumann and Giulia Freer and Marina A. Freudenberg and Marinus C. Lamers and Tadamitsu Kishimoto and Rolf Martin Zinkernagel and Horst Bluethmann and Georges K{\"o}hler},
lNTERLEUKIN-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, acute-phase reaction and haematopoiesis (for reviews see refs 1, 2). In vitro, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and interleukin-11 display overlapping activities with IL-6. This functional redundancy may be explained by the interactions of specific binding receptors with a common signal-transducing receptor (gp130) (for reviews see refs 3, 4). To… 

Immune-neuroendocrine responses to infection in mouse and fish

IL-6-/mice are more susceptible to disseminated candidiasis, and the effect of IL-6 is most likely mediated by neutrophils.

Increased susceptibility to systemic candidiasis in interleukin-6 deficient mice.

IL-6-/- mice are more susceptible to disseminated candidiasis, and the effect of IL-6 is most likely mediated by neutrophils.

IL-6 Knockout Mice

IL-6 has been shown to favour the resolution of infections and to promote optimal humoral responses to various antigens while at the same time being required for the development of immune-mediated diseases, such as CIA or EAE, as well as of diseases caused by improper expansion of specific hematopietic compartments.

Defective inflammatory response in interleukin 6-deficient mice

It is reported here that in the absence of IL- 6, mice are unable to mount a normal inflammatory response to localized tissue damage generated by turpentine injection, and IL-6 is identified as an essential mediator of the inflammatoryresponse to localized inflammation.


Based on the preclinical activity of recombinant human (rh) IL-6, a phase I study in 42 patients with refractory malignancy found flu-like toxicity was observed, and when rhIL-6 was administered after chemotherapy for sarcoma, accelerated platelet recovery was noted in the patients treated with rhIL -6.

IL-6 Unique Functions in Inflammation, Bone Metabolism, and B-Cell Neoplasias Revealed by Studies on IL-6-Deficient Mice

Circulating IL-6 levels are normally very low; however, they are rapidly increased by a number of stimuli such as bacterial or viral infection, tissue damage-induced inflammation, and different kinds of traumas.

Therapeutic uses of anti-interleukin-6 receptor antibody.

Tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, has successfully proved its outstanding efficacy against rheumatoid arthritis, juvenile idiopathic arthritis and Castleman disease, leading to the approval of tocilIZumab for the treatment of these diseases.

Lack of Interleukin-6 Affects IFN-γ and TNF-α Production and Early In Vivo Control of Brucella abortus Infection

It is demonstrated that IL-6 contributes to host resistance during the early phase of B. abortus infection in vivo, and suggested that its protective role maybe partially mediated by proinflammatory immune responses and immune cell recruitment.



Roles of alpha beta and gamma delta T cell subsets in viral immunity.

It is made that alpha beta T-cell memory to viruses is long-lived, and the need for antigen persistence to maintain such memory is questioned, and there is as yet no understanding of the biological significance (if any) of these lymphocytes in viral immunity.

Mice lacking the tumour necrosis factor receptor 1 are resistant to IMF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes

It is reported here that mice homozygous for a disrupted Tnfr l allele (Tnfr1 0) are resistant to the lethal effect of low doses of lipopolysaccharide after sensitization with D-galactosamine, but remain sensitive to high doses oflipopoly Saccharide.

Multiple defects of immune cell function in mice with disrupted interferon-gamma genes.

IFN-gamma is essential for the function of several cell types of the murine immune system and has impaired production of macrophage antimicrobial products and reduced expression of Macrophage major histocompatibility complex class II antigens.

B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes

IL-6 induced a six-to seven-fold increase in proliferation of human thymocytes stimulated with suboptimal doses of PHA, and it is suggested that IL-6 is also an important regulatory of cellular immunity.

Type I IL-1 receptor blockade exacerbates murine listeriosis.

It was found that IL-1 is produced in livers and spleens of mice shortly after the i.v. injection of a sublethal or lethal Listeria monocytogenes inoculum, and evidence showing thatIL-1 plays a role in antibacterial resistance early in listeriosis was obtained through the use of 35F5 mAb.

IgG1 plasmacytosis in interleukin 6 transgenic mice.

The evidence indicates that deregulated gene expression of IL-6 can trigger polyclonal plasmacytosis but cannot induce plasmACYtoma, and it is suggested that additional genetic changes may be required for the generation of plasma cell neoplasia.

Immune response in mice that lack the interferon-gamma receptor.

Mutant mice offer the possibility for the further elucidation of IFN-gamma-mediated functions by transgenic cell- or tissue-specific reconstitution of a functional receptor.

Beta 2-microglobulin-, CD8+ T-cell-deficient mice survive inoculation with high doses of vaccinia virus and exhibit altered IgG responses.

The data indicate that CD8+ lymphocytes are not required to clear high doses of vaccinia virus, and they suggest thatbeta 2m-/- mice are less efficient at antigen-specific IgG production than their beta 2m+/- littermates.

The biology of interleukin-6.

Human IL-6 (BSF2) was originally identified as a factor in the culture supernatants of mitogen or antigen-stimulated peripheral mononuclear cells, which induced immunoglobulin production in Epstein Barr virus transformed B-cell lines or in Staphylococcus aureus Cowan 1 stimulated normal B cells.

Impaired Generation of Anti‐Viral Cytotoxicity against Lymphocytic Choriomeningitis and Vaccinia Virus in Mice Treated with CD4‐Specific Monoclonal Antibody

Injection of CD4‐depleted mice with recombinant interleukin 2 (rIL‐2) partially corrected the impaired virus‐specific cytotoxic T‐cell response, suggesting that IL‐2 supply may be limiting in mice licking T helper cells.