The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 1983-1984

An In Vitro Model of Inflammation and Irritation

Marshall Plaut, MD, and N. Franklin Adkinson Jr., MD
The Johns Hopkins School of Medicine, Baltimore, Maryland

Problem

In vitro models of inflammation have focused on quantitative measurements of stimulus-induced release of mediators from leukocytes, the effector cells in in vivo inflammatory sites. Cells of the monocyte-macrophage lineage respond to a variety of immunologic stimuli, and certain non-immunologic "inflammatory" stimuli, by secreting a variety of biologically active mediators. These mediators range from prostaglandins to lysosomal enzymes. Mediator release is readily quantitated, reproducible, and occurs in a dose-response fashion to specific stimuli.

The researchers propose to correlate the release of prostaglandins from mouse and human macrophages -- like in vitro -- adapted cell lines. Prostaglandins were chosen for study because they appear to be important mediators of the in vivo inflammatory response. The cell lines are homogenous and stable, and some of these cell lines secrete large amounts of prostaglandins in response to a wide variety of stimuli. The researchers intend to identify cell lines which secrete prostaglandins in response to non-immunologic stimuli to define optimal culture conditions which favor this secretory response. They will test a series of agents, including those known to induce contact sensitivity, but which may act non-immunologically, for their capacity to induce prostaglandin secretion from cell lines.

Impact of the Research

The long term goal is to correlate quantitatively in vitro prostaglandin secretion with the capacity of these agents to induce inflammation in vivo. This system may then replace some whole-animal systems in specific testing conditions.