Serial changes in humoral and cellular immunity induced by prostaglandin E2 treatment of murine immune complex...

To examine the mechanism by which prostaglandin E2 (PGE2) inhibits the development of apoferritin (HAF)-induced immune complex glomerulonephritis (ICGN), weekly determinations of glomerular histologic conditions, blood urea nitrogen (BUN), total immunoglobulin levels, anti-HAF antibody, peripheral blood and splenic T cell subsets, and splenic suppressor cell activity were compared between mice receiving HAF and mice additionally treated with PGE2. PGE2 therapy prevented the development of glomerular hypercellularity and the increase in BUN concentration. Administration of PGE2 reduced anti-HAF IgG levels, but total IgM and IgG1, IgG2a, and IgG2b levels were unchanged. Mice receiving HAF alone demonstrated serial reductions in phenotypically identified peripheral blood pan-T cells and suppressor-cytotoxic T cells. PGE2-treated mice maintained normal levels of peripheral blood T cell subsets. Significant reductions in splenic total T cells and suppressor-cytotoxic cells occurred in mice receiving HAF as compared with normal mice. This reduction was offset by an increase in splenic B cells. PGE2 therapy prevented the decrease in splenic T cells at week 1, but not at week 4. Nonspecific suppressor cell activity, as measured by the ability of spleen cells from experimental mice to suppress a mixed lymphocyte reaction (MLR) or to suppress MLR-induced polyclonal IgG synthesis, was not different between the two groups. We conclude that prevention of HAF-ICGN by PGE2 is associated with a reduction in nephritogenic antibody production without an alteration in total immunoglobulin synthesis or the generation of nonspecific suppressor T cells. Changes in the percent of peripheral blood and splenic T cells and B cells may represent an effect of PGE2 on antigen-stimulated B cell proliferation.