Why minocycline can cause systemic lupus - a hypothesis and suggestions for therapeutic interventions based on it.

The tetracycline antibiotic minocycline is widely used in dermatology, but can sometimes cause systemic lupus erythematodes, a serious autoimmune disorder. It is not known how it does this. However, recent data suggest that minocycline can protect cells from apoptosis by inhibition of caspase-dependent and independent cell death pathways. Here, it is suggested that this ability of minocycline is responsible for the induction of lupus. This idea is based on the recent insight that incomplete or failed apoptosis of damaged cells, particularly keratinocytes, may be responsible for the development of auto-immunity. The protection against apoptosis as conferred by minocyclin may be incomplete, with failed apoptosis and development of autoimmunity as a result. Experimental confirmation of the theory may be obtained by in vitro experiments using induction of apoptosis in cell types known to be affected by lupus. Next, mice that are sensitive to apoptosis may be used for in vivo experiments. Novel therapeutic approaches to drug-induced lupus may be based on induction of apoptosis; DNA-damaging immunosuppressive agents appear particularly useful. Such treatments can be tested in apoptosis-deficient mice that develop autoimmune disease.