TreatmentUpdate 55 - Vol. 7, No. 1; January 1995
Sean Hosein

Several research teams have noted a decrease in cell- mediated (CMI) immunity in EGV-infected patients as their CD4+ cell counts fall over time. As well, production of cytokines associated with CMI (interferon-gamma, IL-2 and IL-12) fall in HIV/AIDS while production of cytokines associated with humoral immunity (IL-4, 6, 10) rise. Thus some researchers are suggesting giving subjects with HIV/AIDS extra cytokines that may boost CMI. But the immune systems of such patients are complex and may not necessarily be quickly repaired when they receive supplements of cytokines.

* 27 YEARS OF RESEARCH

One prominent American researcher said that scientists have been studying cytokines for over 27 years and apart from the bone marrow stimulants GM-CSF and EPO, cytokine therapy has not been "terribly successful". This is because cytokines:

- quickly break down - are needed at very small and particular sites - can be toxic when taken in large doses

Some researchers are beginning to suspect that there will not be any single 'magic' cytokine for treating HIV/AIDS. Leading immunologists suspect this is the case because there is usually a 'mix' of cytokines that cause certain effects.

* ANTI-CYTOKINES?

Some doctors think about using cytokines in a "positive" way; that is, giving patients extra cytokines such as IL-2 and interferons. But in lab experiments, adding extra interferon-gamma did not reduce the effect of IL-4 or IL-10, but using anti-IL-4 antibodies did. In mice infected with a virus that gives them AIDS, anti-IL-4 antibodies delayed the development of AIDS.

* TESTING THE THEORY - CANCER

In the section on cancer in this issue of TreatmentUpdate researchers found that anti-IL-6 therapy had weak anti-cancer effects. Their next attempt may include attacking IL-6 and other cytokines, such as IL-10 with chemotherapy.

* TESTING THE THEORY - ARTHRITIS

Researchers in the European Union have used an antibody that attacked the cytokine TNF-alpha (tumor necrosis factor). Subjects in that study received a placebo or the anti-cytokine called cA2. Short-term use of this product improved subjects' quality of life but did not cure their disease.

* MAKING A BLOCKADE

In order for a cytokine to interact with a cell, the cell usually has a receptor to which the cytokine binds (much like a key fitting into and opening a lock). Some researchers suggest that receptor blockers or receptor antagonists should be used to block the effect of certain cytokines on cells. The problem here is that when the receptor for the cytokine gets blocked the body continues to produce high levels of the cytokine. Clearly a more sophisticated approach needs to be developed.

Part of the problem is that researchers don't know how to produce the right mix of cytokines or anti-cytokines that can boost CMI. Without this information some HIV-infected patients and their doctors may resort to using products such as:

- DNCB (TreatmentUpdate 43 and 55)

- Imreg-1 (TreatmentUpdate 24 and 29)

- papaverine (TreatmentUpdate 46 and 48)

- Salk HIV vaccine or Immunogen

that may cause the (delayed-type hypersensitivity) skin reactions that are the sign of cell-mediated immunity. Preliminary results from the Salk HIV vaccine trials will appear in a future issue of TreatmentUpdate.

REFERENCES:

1. Barcellini W, Rizzardi GP. Borghi MO, et al. Th1 and Th2 cytokine production by peripheral blood mononuclear cells from HIV-infected patients. AIDS 1994;8(6):757-762.

2. Bloom B. The power of negative thinking. Journal of Clinical Investigation 1993;91:1265-1266.

3. de Hon FD, Ehlers M, Rose-John S, et al. Development of an interleukin (IL) 6 receptor antagonist that inhibits IL-6-dependent growth of human myeloma cells. Journal of Experimental Medicine 1994;180:2395-2400.

4. Kanagawa O, Vaupel BA, Gayama S, et al. Resistance of mice deficient in IL 4 retrovirus-induced Immunodeficiency Syndrome (MAIDS). Science 1993;262:240-242.

5. Debets R and Savelkoul HFJ. Cytokine antagonists and their potential therapeutic use. Immunology Today 1994;15(10):455458.

6. Elliot MJ, Maini RN, Feldmann MF, et al. Randomized, double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994;344:1105-1110.

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Copyright © 1995 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca