Long-term paracetamol treatment induces interleukin-1β expression in human microglial cells

Abstract

Background : Paracetamol or acetaminophen (N-acetyl-p-aminophenol; APAP) is a widely used as an analgesic and antipyretic drug. This drug has long time been considered as a safe drug, when used in the therapeutic levels. However, the adverse effects concerning long-term APAP usage at the non-hepatotoxicity dosage regarding the human central nervous system, in particular microglia, remains unclear.

Objective : To investigate the effect of short-term (6, 12 and 24 hr.) and long-term APAP treatments (1, 2, 3 and 4 weeks) on the expression of the pro-inflammatory cytokine IL-1β in human microglia.

Design : Experimental research

Setting : Department of Biochemistry and Department of Pathology Faculty of Medicine, Chulalongkorn University

Materials and Methods : Human microglial (CHME-5) cells were cultured in the presence of APAP at the concentration determined by MTS assay for 6, 12 and 24 hr., representing short-term treatment. As for long-term APAP treatment, the cells were cultured with APAP for 1, 2, 3 and 4 weeks. Cell pellets were subsequently collected and the expression of the IL-1β in human microglia was determined by Western Blotting.

Results : The study shows that long-term APAP treatment induces morphological changes in CHME-5 cells. An increase in the number of amoeboid phagocytic cells with shorten processes is demonstrated in the long-term APAP- treated cells since the second week of treatment. Also, the level of IL-1β expression is up-regulated in a time-dependent manner while the short-term treatment shows no alteration, compared to that of control cultured cells.

Conclusions : The results demonstrated that long-term paracetamol treatment activates human microglial cell morphological changes and up-regulates pro-inflammatory cytokine IL-1β expression.