Clinical and immunologic evaluation of HIV-infected patients treated with dinitrochlorobenzene.

BACKGROUND: Promotion of cell-mediated immunity appears to be an important goal in the control of HIV infection. Topical dinitrochlorobenzene (DNCB) stimulates systemic cell-mediated immunity via the induction of cutaneous delayed-type hypersensitivity. OBJECTIVE: Our goal was to evaluate the clinical and immunologic effects of chronic DNCB application in a group of 24 HIV-infected patients. METHODS: We observed the patients for a mean of 28 months (range, 14 to 44 months). Of the 24 patients, 13 continued weekly DNCB application throughout the study (the compliant group), and 11 discontinued DNCB use after a mean of 10.9 months (the noncompliant group). RESULTS: Two of the 13 compliant patients progressed to AIDS; none of these patients died. In contrast, AIDS developed in 5 of the 11 noncompliant patients and four of these patients died. Analysis of lymphocyte subsets revealed significant increases in natural killer cells and activated/cytotoxic CD8 T-cell subsets in the compliant group. In contrast, these cellular immune-related lymphocyte subsets decreased in the noncompliant subjects. Although CD4 T-cell levels decreased in both groups, there was a significantly greater drop in the noncompliant patients. CD8+CD38+ T cells increased significantly in both groups. CONCLUSION: Chronic DNCB application appears to have a beneficial clinical and immunomodulatory effect in HIV-infected patients.

Pilot study of topical dinitrochlorobenzene (DNCB) in human immunodeficiency virus infection.

Dendritic cells, the primary antigen presenting cells of the human immune system, are heavily infected with human immunodeficiency virus (HIV) in patients with the acquired immunodeficiency syndrome (AIDS). Dinitrochlorobenzene (DNCB) is a contact sensitizing agent that acts as a potent immune modulator of dendritic cells. In this pilot study, we examined the safety and efficacy of topical DNCB application in patients with early HIV disease. Topical DNCB was well tolerated by these patients, with an adverse reaction rate of 10%. CD4+ T-cell counts remained stable with repeated DNCB use. In contrast, CD8+ T-cell counts and natural killer cells increased significantly following DNCB sensitization. This increase in CD8+ T-cell and natural killer cell subsets was accompanied by a decrease in HIV replication, as measured by serum HIV RNA levels. Based on this pilot study, we conclude that topical DNCB is safe in early HIV disease and may decrease viral load via a systemic effect on dendritic cells, CD8+ T-cells and natural killer cells. These results require confirmation in larger controlled trials.

Histologic changes in nude mouse skin and human skin xenografts following exposure to sulfhydryl reagents: arsenicals.

This report documents the histological changes in nude mouse skin and in human skin xenografts on nude mice following exposure to phenyldichloroarsine (PDA), a vesicant arsenical. Under light microscopy, we observed in PDA-treated human skin grafts: 1) degeneration of epidermal cell nuclei (apparent by 2 hr after exposure with increasing severity through 48 hr); 2) loss of epidermal cytoplasmic basophilia (apparent by 4 hr, maximal within 12 hr); 3) epidermal cytoplasmic vacuolization (vacuoles appeared within 4 hr and increased in size through 24 hr); 4) cleft formation within the basement membrane zone (apparent by 12 hr, increasing in severity through 24 hr); 5) inflammation evidenced by polymorphonuclear leukocyte (PMN) infiltration (apparent by 4 hr and increasing through 48 hr). The PMNs frequently formed a wall around the lesion, but did not infiltrate the treated area. Nude mouse skin reacted faster to PDA than did the grafts, but the histological changes were similar. Nude mouse hair follicles and sebaceous glands showed similar cellular changes at approximately the same time as did epidermal cells. Transmission electron microscopy of mouse skin exposed to PDA revealed a widening of intercellular spaces with attenuation of desmosomes. The subepidermal clefts resulted from separation within the lamina lucida with the lamina densa forming the base of the cleft. Diphenylchloroarsine caused lesions histologically indistinguishable from those of PDA. Lesions resulting from exposure to other sulfhydryl-binding compounds were very different from arsenical lesions. The arsenical-sensitive cellular constituents were not identified.