Interleukin-2 and the Possibility of Immune Reconstitution


Interleukin-2 and the Possibility of Immune Reconstitution

Being Alive; August 1996
Christopher Griffin

On the second afternoon of the International Conference a meeting was held with the decidedly intriguing title "Immune Reconstitution." Unfortunately, the content of the meeting failed to live up to the promise of its title. The exciting notion of reconstituting an HIV-damaged immune system is an idea way ahead of the science necessary to accomplish this feat. Perhaps a better title would have been "In Search of Immune Reconstitution." For the search goes on, and there's a long way yet to go.

This meeting focused primarily on the immunomodulator interleukin-2 (IL-2) and its success in increasing levels of CD4 cells in people with HIV/AIDS. IL-2 is produced naturally in the body by T-cells and has potent effects on the proliferation and differentiation of a number of immune cells, including T-cells, B-cells and natural killer cells. The commercial and trial form of IL-2 is produced by recombinant DNA technology. It is licensed for treatment of kidney cancer, but is being investigated as an agent for boosting an AIDS-damaged immune system.

Results of several trials showed that the administration of IL-2, either in periodic intravenous infusions (CIV IL-2) or subcutaneous (under the skin) injections (scPEG IL-2), had a significant positive impact upon the participants' levels of CD4 cells, and can be generally well-tolerated, despite transient yet pronounced side effects.

Dr. Richard T. Davey, senior investigator in the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases (NAIAD), presented preliminary findings from an ongoing phase II trial of subcutaneously self-injected IL-2 that show dramatic increases in levels of CD4's in people with early HIV infection (over 500 CD4's). All were already taking antiretroviral drugs, and all were taught to give themselves the injections of the drug. Several dosages and schedules of subcutaneous IL-2 were studied, the most effective of which was 7.5 million international units twice a day for five days every four weeks. T-cells in this group increased from an average of 670 at baseline to 1488 at six months.

"Our data suggest," said Dr. Davey, "that therapy with subcutaneous IL-2, in combination with antiretroviral drugs, has the potential to halt the usual progression of HIV disease by maintaining a person's CD4 cell count in the normal range for prolonged periods of time. The CD4 cell increases we have seen...have been similar to those previously achieved with intravenous infusions, but with fewer side effects. The subcutaneous regimen allows patients to self-administer their medication on an outpatient basis. Further studies are needed to help discern whether the increases in CD4 counts will translate to clinical benefit."

Dr. Andrew Carr of St. Vincent's Hospital, Sydney, Australia, presented results of a study he performed to determine the safety and immunological effects of periodic continuous intravenous IL-2 plus antiviral therapies, compared with subcutaneous IL-2 plus antivirals, and compared with antiviral therapy alone. This trial involved 150 HIV+ individuals with CD4 levels of 200-500 cells/mm. Two thirds of the study participants were receiving antiretroviral monotherapy, the remaining receiving antiviral combination therapy. A significant increase in baseline CD4 counts was observed with both IL-2 preparations. Changes in CD4 count were almost 450 cells for the intravenous and 130 cells for the subcutaneous group; the control group (antiviral therapy only) registered a decline of approximately 70 CD4s.

Side effects from IL-2, either intravenous or subcutaneous, are reported to be pronounced: "flu-like symptoms," fatigue, aches and pains, headache, and/or nausea, setting in after three or four days of treatment, resolving within 48 hours of the end of treatment. There has been some concern that IL-2 side effects would prove too severe for people with HIV-damaged systems, but a 14-month study on the quality of life associated with IL-2 treatments conducted by Bill Barrick, head nurse at NAIAD, found no overall difference in quality of life or symptom distress among people receiving IL-2 and those not receiving it.


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