Suramin Affects Human Peripheral Blood Mononuclear Cells in vitro: Inhibition of T Cell Growth and Modulation of Cytokine Secretion

Abstract

Suramin, a polyanionic compound, which has been in clinical use for the treatment of African trypanosomiasis for several decades, has recently been introduced in clinical oncology. Its effects on the immune system seemed therefore of interest. In the present study we tried to elucidate in vitro how suramin affected different functions of human peripheral blood mononuclear cells (PBMC). Suramin suppressed the proliferation of PBMC in response to various stimuli, including OKT3, phytohemagglutinin (PHA), phorbolmyristateacetate (PMA) and ionomycin, purified protein derivate of Mycobacterium tuberculosis (PPD) and antibodies against CD2. It also inhibited the binding of monoclonal antibodies to T cell surface antigens. This effect was not dependent on the isotype of the antibody, but seemed to be highly epitope-specific. Among a panel of antibodies against one antigen, only a few were affected by the compound. Whereas the binding of Leu3a and OKT3 was for instance fully suppressed by suramin, OKT4 and Leu4 binding was only slightly affected. Suramin also decreased the expression of T cell surface molecules such as CD2, CD25 and CD4 in preactivated PBMC and had pronounced effects on cytokine production. Interestingly the compound had adverse regulatory effects on different cytokines. Whereas the secretion of interferon-γ was completely suppressed by suramin, interleukin-2 (IL-2) and IL-4 production was stimulated. These results demonstrate that suramin affects T cell function in multiple different ways. This will have to be considered, when suramin is used in the treatment of cancer patients.

Ciliary Body Toxicity of Subconjunctival Suramin Compared with Mitomycin-C in the Rabbit Eye: Determining the Toxic Concentration

“…However, competitive inhibition of growth factors is not the only mode of action for suramin. Suramin also acts by inhibiting intracellular secondary messengers and many intranuclear enzymes and it is speculated to have immunosuppressive properties that suppress inflammation following tissue damage [32] . We have also previously shown that, similar to MMC, suramin causes fibrosis, decreased collagen-III deposition, decreased infiltration of T lymphocytes and, to a lesser extent, of macrophages and B lymphocytes [20] .…”