Study re: Minocycline's Effects on T Cells

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Thu Mar 18 07:39:42 2010 Pacific Time

Acne Drug Prevents HIV Breakout

BALTIMORE, March 18 (AScribe Newswire) -- s Hopkins scientists

have found that a safe and inexpensive antibiotic in use since the 1970s for

treating acne effectively targets infected immune cells in which HIV, the

virus that causes AIDS, lies dormant and prevents them from reactivating and

replicating.

The drug, minocycline, likely will improve on the current treatment

regimens of HIV-infected patients if used in combination with a standard

drug cocktail known as HAART (Highly Active Antiretroviral Therapy),

according to research published now online and appearing in print April 15

in The Journal of Infectious Diseases. " The powerful advantage to using

minocycline is that the virus appears less able to develop drug resistance

because minocycline targets cellular pathways not viral proteins, " says

Janice Clements, Ph.D., Wallace Stanton Professor of Faculty Affairs,

vice dean for faculty, and professor of molecular and comparative

pathobiology at the s Hopkins University School of Medicine.

" The big challenge clinicians deal with now in this country when

treating HIV patients is keeping the virus locked in a dormant state, "

Clements adds. " While HAART is really effective in keeping down active

replication, minocycline is another arm of defense against the virus. "

Unlike the drugs used in HAART which target the virus, minocycline

homes in on, and adjusts T cells, major immune system agents and targets of

HIV infection. According to Clements, minocycline reduces the ability of T

cells to activate and proliferate, both steps crucial to HIV production and

progression toward full blown AIDS.

If taken daily for life, HAART usually can protect people from

becoming ill, but it's not a cure. The HIV virus is kept at a low level but

isn't ever entirely purged; it stays quietly hidden in some immune cells. If

a person stops HAART or misses a dose, the virus can reactivate out of those

immune cells and begin to spread.

The idea for using minocycline as an adjunct to HAART resulted when

the Hopkins team learned of research by others on rheumatoid arthritis

patients showing the anti-inflammatory effects of minocycline on T cells.

The Hopkins group connected the dots between that study with previous

research of their own showing that minocycline treatment had multiple

beneficial effects in monkeys infected with SIV, the primate version of HIV.

In monkeys treated with minocycline, the virus load in the cerebrospinal

fluid, the viral RNA in the brain and the severity of central nervous system

disease were significantly decreased. The drug was also shown to affect T

cell activation and proliferation.

" Since minocycline reduced T cell activation, you might think it

would have impaired the immune systems in the macaques, which are very

similar to humans, but we didn't see any deleterious effect, " says

Szeto, a graduate student in the Department of Cellular and Molecular

Medicine working in the Retrovirus Laboratory at Hopkins. " This drug strikes

a good balance and is ideal for HIV because it targets very specific aspects

of immune activation. "

The success with the animal model prompted the team to study in test

tubes whether minocycline treatment affected latency in human T cells

infected with HIV. Using cells from HIV-infected humans on HAART, the team

isolated the " resting " immune cells and treated half of them with

minocycline. Then they counted how many virus particles were reactivated,

finding completely undetectable levels in the treated cells versus

detectable levels in the untreated cells.

" Minocycline reduces the capability of the virus to emerge from

resting infected T cells, " Szeto explains. " It prevents the virus from

escaping in the one in a million cells in which it lays dormant in a person

on HAART, and since it prevents virus activation it should maintain the

level of viral latency or even lower it. That's the goal: Sustaining a

latent non-infectious state. "

The team used molecular markers to discover that minocycline very

selectively interrupts certain specific signaling pathways critical for T

cell activation. However, the antibiotic doesn't completely obliterate T

cells or diminish their ability to respond to other infections or diseases,

which is crucial for individuals with HIV.

" HIV requires T cell activation for efficient replication and

reactivation of latent virus, " Clement says, " so our new understanding about

minocyline's effects on a T cell could help us to find even more drugs that

target its signaling pathways. "

The research was supported by grants from the National Institutes of

Health. Authors of the paper, in addition to Clements and Szeto, are

K. Brice, Sheila A. Barber and F. Siliciano, all of s Hopkins.

Also, Hung-Chih Yang of National Taiwan University Hospital.

On the Web:

http://www.hopkinsmedicine.org/mcp/faculty_webpages/clements.html

http://www.hopkinsmedicine.org/mcp/Retrovirus/

http://www.journals.uchicago.edu/toc/jid/current

Related Video:

Janice E.

Clements, Ph.D., on her team's discovery that a safe, inexpensive antibiotic

will improve on the current treatment regimens of HIV-infected patients.