Biomedical Frontiers: Fall 1996, Vol.4, No.1
Trials Investigate Phototherapy and HIV

Two FDA-sponsored multicenter clinical trials now under way at CPMC are examining the effect of phototherapy--ultraviolet light to treat skin disorders--on the immune system and the progression of HIV disease.

Dermatologists regularly use phototherapy to treat a number of skin disorders, including psoriasis and atopic dermatitis. In HIV-positive patients, phototherapy is often used to also treat pruritus and eosinophilic pustular folliculitis. But there is evid ence that phototherapy is immunosuppressive. Studies have shown that ultraviolet light activates viruses, such as herpes simplex virus in skin lesions. This brings into question the safety of treating HIV-positive patients with phototherapy.

One multicenter clinical trial now under way is examining the blood of HIV-positive and HIV-negative patients undergoing phototherapy. Dr. Elizabeth Knobler, assistant professor of clinical dermatology, and colleagues are enrolling patients. The blood of these patients will be studied before, during, and after phototherapy. Specifically, the study will look at the effect of ultraviolet B (UVB) on cytokine production. Cytokines are protein hormones, produced by different cell types, which act on many other cells. Effects on the cytokines interleukin- (IL) 2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor, and interferon gamma will be examined. A photo-induced shift in the production of these cytokines would provide some clues as to how ultraviolet l ight affects the immune system, says Dr. Knobler. For instance, studies have shown that as HIV disease progresses, IL-2 levels decrease while levels of IL-6 and IL-10 increase. If ultraviolet light produces a similar shift, it may be evidence that UV play s a role in accelerating the progression of HIV disease.

used by permission of Seragen Inc. (adapted by Jodi Miller/H Roberts Design)

A second FDA-sponsored trial will examine the effects of UVB as well as PUVA (psoralen and ultraviolet A) on HIV disease. To date, a few short-term observations have revealed no obvious detrimental effects of UV exposure on HIV disease progression. In thi s trial, researchers are examining HIV load, CD4 and CD8 lymphocyte counts, and various other parameters of HIV disease.

Dr. Knobler, together with Dr. William Sherman, associate professor of clinical medicine, is also involved in a multicenter study of the effectiveness of a new "fusion protein" to treat cutaneous T cell lymphoma (CTCL). The fusion protein, developed by Se ragen, is known as DAB-IL-2 and is a complex of the cytokine IL-2 bound to diphtheria toxin. About half of patients with CTCL express the receptor for IL-2 on the surface of their T cells. The researchers will treat patients whose malignant cells express the receptor. DAB-IL-2 binds to the expressed receptor, prompting the cell to ingest the entire DAB-IL-2 complex. The diphtheria toxin would then destroy the cell, perhaps relieving disease symptoms.