Administration in vivo of recombinant interleukin 2 protects mice against septic death.

نویسندگان

  • C Weyand
  • J Goronzy
  • C G Fathman
  • P O'Hanley
چکیده

Administration in vivo of recombinant interleukin 2 (rIL-2) to mice induces a polyclonal IgM response. When co-administered with a specific antigen, rIL-2 can enhance concentrations of murine IgM antibodies specific for the antigen by fivefold within 7 d of initial treatment. IgM antibodies that are induced after injection of rIL-2 include antibodies specific for J5, a cell wall core lipopolysaccharide (LPS) antigen that is shared by the different members of the Enterobactericeae family. We report here that mice pretreated with rIL-2 or immunized with J5 antigen 7 d before bacterial challenge were protected from septic death that is caused by intraperitoneal challenges with Escherichia coli. Optimal protection was provided by a combined J5 antigen and rIL-2 treatment. Acquisition of the rIL-2 and J5 antigen-induced protection against lethal bacterial infection coincided temporally with maximal serum IgM titers that also contained IgM antibodies specific for the J5 antigen. In passive immunization experiments, the affinity-purified IgM fraction in sera of rIL-2-treated animals was identified as necessary and sufficient for protection. The IgM-depleted serum had no protective effect. The nonspecific augmentation of host-defense mechanisms without the induction of endotoxin manifestations makes rIL-2 a potential candidate to any alternative LPS-containing vaccines for the prevention of bacterial infections by gram-negative organisms since the core LPS antigen is shared among gram-negative bacteria.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Interferon β protects against lethal endotoxic and septic shock through SIRT1 upregulation

Lipopolysaccharide (LPS), an endotoxin derived from gram-negative bacteria, promotes the secretion of proinflammatory cytokines and mediates endotoxemia through activation of mitogen activated protein kinases, NF-κB, and interferon regulatory factor-3. Silent information regulator transcript-1 (SIRT1), an NAD-dependent deacetylase, mediates NF-κB deacetylation, and inhibits its function. SIRT1 ...

متن کامل

Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia

Because of its ability to efficiently inhibit in vitro cytokine production by activated macrophages, we hypothesized that interleukin (IL) 10 might be of particular interest in preventing endotoxin-induced toxicity. We therefore examined the effects of IL-10 administration before lipopolysaccharide (LPS) challenge in mice. A marked reduction in the amounts of LPS-induced tumor necrosis factor (...

متن کامل

Pretreatment with recombinant murine tumor necrosis factor alpha/cachectin and murine interleukin 1 alpha protects mice from lethal bacterial infection

Tumor necrosis factor/cachectin (TNF/C) is the principal mediator of bacterial endotoxin-induced shock and death. We found that the C3H/HeJ mouse, which is less able to produce TNF/C in response to endotoxin, has a 1,000-fold greater susceptibility to lethal infection with Escherichia coli than the TNF-responsive congenic mouse, C3H/HeN. This surprising finding suggested that this lethal peptid...

متن کامل

Coenzyme Q10 Protects Hippocampal Neurons against Ischemia/ Reperfusion Injury via Modulation of BAX/Bcl-2 Expression

Introduction: Preliminary studies have con.rmed reduction in cell death following treatment with antioxidants. According to this .nding we study the relationship between consumption of CoQ10 and expression of Bax and Bcl2 in hippocampus following ischemia/reperfusion as proteins involved in cell programmed death or apoptosis. Methods: We studied the protective role of CoQ10 against ischemia-rep...

متن کامل

PRETREATMENT WITH RECOMBINANT MURINE TUMOR NECROSIS FACTOR cdCACHECTIN AND MURINE INTERLEUKIN 1 a PROTECTS MICE FROM LETHAL BACTERIAL INFECTION

Tumor necrosis factor a/cachectin (TNF/C) is a well-characterized peptide (1) that may, through its diverse effects on cells, mediate many normal host functions, including tissue remodeling and the mobilization of energy reserves required by the infected host (2). In contrast to such beneficial effects, TNF/C has also been shown to have adverse effects on the animal host . It is a principal med...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of clinical investigation

دوره 79 6  شماره 

صفحات  -

تاریخ انتشار 1987