AEGiS-CATIE: Protease inhibitors: shutting down HIV by suppressing cytokines

Protease inhibitors: shutting down HIV by suppressing cytokines

TreatmentUpdate84 - Vol. 9, No. 10 - pp. 2-3; December, 1997
Sean Hosein

Summary

Cytokines are chemicals used by cells of the immune system to send signals to each other. Different cytokines, such as interleukin-2 and interferon-alpha, send different messages. High levels of some cytokines appear to promote high levels of HIV production. That is why some researchers want to test drugs that reduce cytokine levels and in turn suppress HIV. Drugs which can suppress cytokine production include:

* cyclosporin

* corticosteroids

* interleukin-10

* thalidomide.

Now researchers have found that the protease inhibitor ritonavir can suppress production of the cytokines TNF-alpha (tumour necrosis factor), interleukins-1-alpha and -beta and interleukin-6. By keeping levels of these chemical messengers low, ritonavir also suppresses production of HIV. These results may encourage pharmaceutical companies to search for anti-inflammatory drugs that can selectively suppress the cytokines mentioned above, which could prove useful for the treatment of PHAs.

Study Details and Results

For their experiments, researchers used monocytes, a type of cell that is not quickly killed when infected by HIV. Researchers think that monocytes/macrophages, and not T cells, are the main target and breeding ground for HIV. Although HIV infected the cells in the experiment, the infection proceeded "quietly." When technicians exposed the cells to cytokines such as TNF, the infection flared and levels of HIV rose by as many as 200 times. Yet exposure to large concentrations of ritonavir then shut down production of HIV.

This study shows that maintaining an adequate level of a protease inhibitor can suppress production of certain cytokines and, in turn, HIV, which provides another reason to take these drugs on a regular basis. The suppression of inflammatory cytokines by protease inhibitors may help explain the long-term benefits of these drugs.

REFERENCES:

1. Al-Harthi L, Roebuck KA, Kessler H and Landay A. Inhibition of cytokine-driven Human immunodeficiency virus type 1 replication by a protease inhibitor. Journal of Infectious Diseases 1997;176:1175-1179.

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