Hydroxyurea exerts a cytostatic but not immunosuppressive effect on T lymphocytes

Abstract

Hyper-proliferation of T-lymphocytes is a major factor contributing to HIV pathogenesis. HU exerts a cytostatic effect on T lymphocytes, without altering their activation and apparently without having an immunosuppressive effect. The increase in cytokine production at the single cell level might compensate for the decrease in the percentage of activated CD4 T lymphocytes, without overall impairment of HIV-specific immune responses.

New bis(thiosemicarbazonate) gold(III) complexes inhibit HIV replication at cytostatic concentrations: Potential for incorporation into virostatic cocktails

“…S2e and f). HU has been reported to exert a cytostatic but not an immunosuppressive effect on T lymphocytes by not decreasing the production of T helper (h)1 or Th2 cytokines [42]. In our experience 4 did not affect TNF-α and IFN-γ (both Th1 cytokines) production.…”

Virostatics: A New Class of Anti-HIV Drugs

“…Instead, hydroxyurea should not be used with stavudine, because of the demonstrated toxicity of this combination [35], nor with tenofovir, as data from our group show that in an animal model didanosine, tenofovir and hydroxyurea combination is fairly toxic (unpublished). enhanced by hydroxyurea after both Th-1 and Th-2 stimulation [57].…”

“…In fact one of the main concerns regarding the use of this combination in the clinical setting is that in patients treated with didanosine plus hydroxyurea the CD4 cell count increase was blunted compared to its antiviral effects. However, data from different groups have conclusively demonstrated that hydroxyurea blocks cellular proliferation but does not impede cellular activation nor diminish recall responses [57][58][59]. In a recent in vitro study [57] hydroxyurea reduced cell proliferation of both CD4 + and CD8 + T lymphocytes in a linear dose dependent manner.…”

“…However, data from different groups have conclusively demonstrated that hydroxyurea blocks cellular proliferation but does not impede cellular activation nor diminish recall responses [57][58][59]. In a recent in vitro study [57] hydroxyurea reduced cell proliferation of both CD4 + and CD8 + T lymphocytes in a linear dose dependent manner. The activation profile of total T lymphocytes, CD8 and CD4 T cell subsets were monitored for the expression of three surface activation markers: CD69, CD25, and HLA-DR. No relevant differences between treated and untreated controls were observed regarding these markers.…”

Immunotherapeutic Restoration in HIV-Infected Individuals

“…This combination has immune modulating activity and reduces viral targets (such as CD4 + T lymphocytes), possibly with limited immunosuppressive effects. Regarding the concerns of immunosuppressive effects of HU, several studies have demonstrated that HU blocks cellular proliferation but does not impede cellular activation nor diminish recall response [140,141]. In addition, suppression of immune activation by cytostatic drugs, such as HU, could complement cART.…”