Related Experiment Videos
Interleukin-2 increases the oxidative activity and induces migration of murine polymorphonuclear leukocytes in vivo
1Cetus Corporation, Emeryville, CA 94608.
Abstract:
Since recombinant human interleukin-2 (IL-2) can protect mice from a lethal bacterial challenge and can induce a vascular leak, we investigated the effects of IL-2 on the oxidative metabolism and migration of murine polymorphonuclear leukocytes (PMN) in vivo. To assess oxidative activity of PMN, we used luminol-dependent chemiluminescence (CL) to measure oxygen radical formation after stimulation of the PMN with phorbol myristate acetate (PMA). We demonstrated that single IP doses of IL-2, from 0.2-3 mg/kg, could significantly increase CL from peripheral blood PMN obtained after IL-2 treatment. The increase of PMN-CL induced by IL-2 in vivo reached a maximum 4.5 fold increase at 3 and 6 h after IL-2 treatment. At 1, 12, and 24 h after rIL-2 treatment, there were no changes in CL and PMN activity remained within normal limits. Intraperitoneally administered IL-2 also caused a significant influx of PMN into the peritoneal cavity. IL-2 increased the percentage of PMN among the peritoneal exudate cells from a control baseline level of less than 1% to 18% PMN after IL-2 treatment. These data that demonstrate the capacity of IL-2 to augment the function and metabolism of PMN in vivo and illustrates the broad range of effects of IL-2 on the immune system in vivo and may explain in part the protective effects of IL-2 in experimental bacterial infections and the possible role of PMN in the systemic toxicities induced by IL-2.
Insights
Recombinant human interleukin-2 (IL-2) enhances polymorphonuclear leukocyte (PMN) oxidative activity and migration in mice. This immune system modulation may explain IL-2
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Recombinant human interleukin-2 (IL-2) exhibits protective effects against bacterial infections and can induce vascular leakage.
- The precise mechanisms by which IL-2 influences immune cell function in vivo remain incompletely understood.
Purpose of the Study:
- To investigate the effects of IL-2 on the oxidative metabolism and migration of murine polymorphonuclear leukocytes (PMN) in vivo.
- To elucidate the role of PMN activation in IL-2's protective and toxic effects.
Main Methods:
- Murine model treated with single intraperitoneal doses of IL-2 (0.2-3 mg/kg).
- Assessment of PMN oxidative activity using luminol-dependent chemiluminescence (CL) after phorbol myristate acetate (PMA) stimulation.
- Quantification of PMN migration into the peritoneal cavity via analysis of peritoneal exudate cells.
Main Results:
- IL-2 treatment significantly increased PMN chemiluminescence (CL), indicating enhanced oxygen radical formation, with a peak 4.5-fold increase at 3-6 hours post-treatment.
- A significant influx of PMN into the peritoneal cavity was observed, increasing from <1% to 18% of peritoneal exudate cells.
- PMN activity and CL returned to baseline levels by 12-24 hours after IL-2 administration.
Conclusions:
- IL-2 administration augments PMN oxidative metabolism and promotes PMN migration in vivo.
- These findings suggest that IL-2's effects on PMN function contribute to its protective role in bacterial infections and potentially to its systemic toxicities.