In vitro immunomodulatory properties of tucaresol in HIV infection.

Abstract

The immunomodulatory properties of tucaresol (compound 589C80) were tested on in vitro antigen- and mitogen-stimulated proliferation and cytokine production by peripheral blood mononuclear cells (PBMC) of HIV-infected individuals and healthy controls (HC). Results showed that tucaresol: (1) increases influenza A virus-, gp 160 peptide-, and HLA alloantigen-stimulated proliferation as well as interleukin (IL)-2 and interferon gamma (IFN gamma) production by PBMC of HIV-infected individuals with higher CD4 counts (>500/microl) but had only a marginal immunomodulatory effect on PBMC of patients with lower CD4 counts (<500/microl); (2) did not modify IL-10 production; (3) augmented CD25 expression on mitogen-stimulated T cells of HC but not of HIV-infected individuals; and (4) marginally increased CTL activity. The immunomodulatory properties of tucaresol were confirmed by PCR analyses; additional data showed that tucaresol costimulated CD3-dependent triggering of T cells and that this stimulation was independent of CD28 costimulation. The immunomodulatory effects of tucaresol on T cell functions are characterized by a bell-shaped dose response curve; the action of the compound is optimal in the 100 to 300 microM range. Analyses of mitogen-stimulated apoptosis demonstrated that the lack of effect of tucaresol at higher doses is not the result of increased cell death, suggesting a role of functional impairment. These data confirm that tucaresol can stimulate T helper cell function and enhance the production of type 1 cytokines, thus eliciting cell-mediated immunity, and warrant its potential utility in the therapy of HIV infection.

• Authors: M Clerici, M Cogliati, G Rizzardini, F Colombo, S Fossati, J Rhodes, D Bray, S Piconi
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 97 Issue 3 Pg. 211-20 (Dec 2000) ISSN: 1521-6616 [Print] United States
• PMID: 11112360 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• Adjuvants, Immunologic
• Antigens
• Benzaldehydes
• Benzoates
• Interleukin-2
• RNA, Messenger
• Receptors, Interleukin-2
• Interferon-gamma
• tucaresol

Topics

• Adjuvants, Immunologic (pharmacology)
• Antigens (pharmacology)
• Apoptosis (drug effects)
• Benzaldehydes (immunology, pharmacology)
• Benzoates (immunology, pharmacology)
• CD4-Positive T-Lymphocytes (chemistry)
• CD8-Positive T-Lymphocytes (drug effects)
• Cell Division (immunology)
• HIV Infections (drug therapy)
• Humans
• Interferon-gamma (biosynthesis, metabolism)
• Interleukin-2 (biosynthesis, genetics)
• Leukocytes, Mononuclear (chemistry, drug effects, metabolism)
• RNA, Messenger (drug effects, metabolism)
• Receptors, Interleukin-2 (analysis, genetics)