Modulation of the proliferative response of murine thymocytes stimulated by IL-1, and enhancement of IL-1 beta secretion from mononuclear phagocytes by tetracyclines

Abstract

The capacity of minocycline and tetracycline for modulation of IL-1 secretion by LPS-stimulated human monocytes was investigated in vitro. Both minocycline and tetracycline suppressed the murine thymocyte co-mitogenic bioassay of IL-1 at 2 and 4 mg/l respectively. IL-1 beta secretion by LPS-stimulated human monocytes cultured for 24h at 1 x 10(6)/ml with 0, 5, 10 and 50 mg/l minocycline or tetracycline was therefore determined by ELISA. Monocytes from five different individuals served as replicates. LPS-stimulated monocytes secreted significantly more IL-1 beta in the presence of minocycline (P less than 0.01, 2-way analysis of variance). There was no difference in the enhanced levels of IL-1 beta secreted with 5 mg/l minocycline compared with 50 mg/l minocycline. Loss of viability could only be associated with enhanced IL-1 beta release by monocytes with 50 mg/l minocycline. Although tetracycline enhanced IL-1 beta secretion in four of the five replicate experiments, this did not prove significant owing to the large error variance between individual monocyte cultures. Thus, therapeutic levels of tetracyclines, especially minocycline, modulate mononuclear cell activities in vitro.