Long before AIDS appears, researchers can find subtle defects in the way the immune system works. For example, over time, HIV-infected people appear less able to produce certain chemical messengers (cytokines) needed by the immune system. These cytokines include:
This trio of chemicals is necessary for the immune system to fight many of the infections and cancers seen in HIV/AIDS. The type of immune response that uses these cytokines is called cellular immunity. Although levels of these cytokines appear to decrease over time, levels of other cytokines rise. These latter cytokines include:
Relatively high levels of these three cytokines hamper the immune system's ability to fight AIDS-related infections. Researchers aren't sure why this change in cytokine production occurs, but it may be caused by continuous exposure to HIV and its proteins. People who have been infected with HIV for many years, but whose immune systems do not degrade, appear to maintain their ability to produce IFN-gamma and other important cytokines. Changes in cytokine levels have also been noticed by drug companies that have made synthetic versions of IL-2, IFN-gamma and IL-12. These synthetic versions are being tested in clinical trials involving people with AIDS and others with cancer.
HAART is the term given to a combination of protease inhibitors and drugs such as efavirenz and nevirapine in combination with AZT and similar chemicals. People treated with HAART tend to have increased CD4+ cell counts and decreased levels of HIV. Moreover, previously difficult-to-treat infections often go into remission. Researchers aren't certain why all of these events occur, but it is likely that the decreased level of HIV puts a stop to damage caused by the virus to the immune system. The dramatic fall in viral load then gives the immune system a chance to repair itself.
In the next article we look at the impact of HIV infection on the creation of certain cytokines and at the effect of HAART on this process.
1. Musey LK, Kreiger JN, Hughes JP, et al. Early and persistent Human Immunodeficiency Virus Type 1 (HIV-1)-specific T helper dysfunction in blood and lymph nodes following acute HIV-1 infection. Journal of Infectious Diseases 1999;180:278-284.
2.Vingerhoets J, Visalinkumi E, Penne G et al. Altered receptor expression and decreased sensitivity of T-cells to the stimulatory cytokines IL-2, IL-7 and IL-12 in HIV infection. Immunology Letters 1998;61:53-61.
3. Barcova M, Kacani L, Speth C and Dierich M. gp41 envelope protein of Human Immunodeficiency Virus induces interleukin-10 (IL-10) in monocytes but not in B, T or NK cells, leading to reduced IL-2 and interferon-gamma production. Journal of Infectious Diseases 1998;177:905-913.
4. Klein SA, Dobmeyer JM, Dobmeyer TS, et al. Demonstration of the Th1 to Th2 cytokine shift during the course of HIV-1 infection using cytoplasmic cytokine detection on single cell level by flow cytometry. AIDS 1997;11:1111-1118.
5. Nicastri E, Sarmati L, Ercoli L, et al. Reduction of IFN-gamma and IL-2 production by peripheral lymphocytes of HIV-exposed seronegative subjects. AIDS 1999;13(11):1333-1336.
6. Kelleher P, Maroof A and Knight SC. Retrovirally induced switch from production of IL-12 to IL-4 in dendritic cells. European Journal of Immunology 1999;29(7):2309-2318.
7. Saha K, Volsky DJ and Matczak E. Resistance against syncytium-inducing Human Immunodeficiency Virus Type 1 (HIV-1) in selected CD4+ T cells from an HIV-1-infected nonprogressor: evidence of a novel pathway of resistance mediated by a soluble factor(s) that acts after virus entry. Journal of Virology 1999;73(9):7891-7898.
8. Benyoucef S, Lion G, Gérard Y, et al. Imbalance in cytokine production by whole blood related to presence of cytopathogenic HIV-1 strains in HIV-1-infected patients. Infection 1998;26(2):109-112.
9. Imami N, Antonopoulos C, Hardy GAD,e t al. Assessment of Type 1 and Type 2 cytokines in HIV Type-1-infected individuals: impact of Highly Active Antiretroviral Therapy. AIDS Research and Human Retroviruses 1999;15(17):1499-1508.
10. Cattelan AM, Calabro ML, Aversa SML, et al. Regression of AIDS-related Kaposi's sarcoma following antiretroviral therapy with protease inhibitors: biological correlates of clinical outcome. European Journal of Cancer 1999;35(13):1809-1815.
20000101
CATE10402
Copyright © 2000 - 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.
ÆGiS is made possible through unrestricted grants from Boehringer Ingelheim, Elton John AIDS Foundation, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2000. This material is designed to support, not replace, the relationship that exists between you and your doctor.
ÆGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1990, 2000. ÆGiS & the Sisters of Saint Elizabeth of Hungary. All materials appearing on ÆGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of ÆGIS, or the party credited as the provider of the content.