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

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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-1β secretion by LPS-stimulated human monocytes cultured for 24 h at 1 × 104/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-1β in the presence of minocycline (P > 0.01, 2-way analysis of variance). There was no difference in the enhanced levels of IL-1β secreted with 5 mg/l minocycline compared with 50 mg/l minocycline. Loss of viability could only be associated with enhanced IL-1β release by monocytes with 50 mg/l minocycline. Although tetracycline enhanced IL-1β 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.