MODULATION OF THE DEVELOPMENT OF HUMORAL IMMUNITY BY TOPICALLY APPLIED ACETONE, ETHANOL, AND 12-O-TETRADECANOYLPHORBOL-13-ACETATE

The effects of topically applied 12-O-tetradecanoylphorbol-13-acetate (TPA), acetone, and ethanol on systemic immune function were analyzed in SSIN mice. A total of one, four, or eight dorsal applications of so lvent (50-300 mu l/treatment, 2x/week) affected neither the overall ce llularity of the spleen nor the relative proportions of splenic cells expressing CD4, CD8, or Ig surface markers. In contrast, overall cellu larities of the spleen increased and relative T cell content of the sp leen decreased in mice treated multiple times with TPA (2 mu g/applica tion in 0.2 mi acetone). The development of splenic B cells secreting IgM against sheep red blood cells (SRBC, a T-cell-dependent antigen) w as retarded, and the overall duration of IgM synthesis was decreased, in mice immunized 1 hr after the last of four applications (>200 mu l) of either solvent. Comparable retardations occurred in mice immunized as late as 7 days after termination of solvent treatment. However, so lvent effects on the development of antibody-forming cells were not ob served after eight topical applications or when TNP-LPS (a T-cell-inde pendent antigen) was used as the immunogen. The effects of TPA on the development of IgM-secreting B cells were indistinguishable from those of the solvent used for its application. Although serum hemagglutinat ion titers to SRBC correlated with the relative numbers of splenic B c ells producing IgM, in vitro proliferative responses to B and T cell m itogens were not predictive of the effects of solvents or TPA on the d evelopment of antibody-secreting cells. Collectively, these studies de monstrate that topically applied acetone and ethanol can systemically modulate humoral immunity and emphasize the need for inclusion of non- treated controls when assessing the potential immunomodulatory activit ies of agents dissolved in acetone or ethanol. (C) 1996 Society of Tox icology