Editors' ChoicePharmacology

HIV Drugs Can Dampen Inflammation, Too

Sci. Signal.  25 Nov 2014:
Vol. 7, Issue 353, pp. ec330
DOI: 10.1126/scisignal.aaa3395

Nucleoside reverse transcriptase inhibitors (NRTIs) stop HIV in its tracks by blocking reverse transcription, a process critical for HIV to replicate its genome. Fowler et al. found that in mice, these drugs also block inflammation caused by a large protein complex called the NLRP3 inflammasome. This activity is independent of the drugs' ability to block reverse transcription. Instead, the drugs block the activity of the ion channel P2X7, which activates the NLRP3 inflammasome. NRTIs improved outcomes in several NLRP3 inflammasome-dependent mouse models of inflammation, including age-related macular degeneration and graft-versus-host disease.

B. J. Fowler, B. D. Gelfand, Y. Kim, N. Kerur, V. Tarallo, Y. Hirano, S. Amarnath, D. H. Fowler, M. Radwan, M. T. Young, K. Pittman, P. Kubes, H. K. Agarwal, K. Parang, D. R. Hinton, A. Bastos-Carvalho, S. Li, T. Yasuma, T. Mizutani, R. Yasuma, C. Wright, J. Ambati, Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity. Science 346, 1000–1003 (2014). [Abstract] [Full Text]

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