Altered production of tumour necrosis factors alpha and beta and interferon gamma by HIV-infected individuals

Abstract

SUMMARY: In vitro studies shows that recombinant tumour necrosis factor (TNF) α and β, and interferon-gamma (IFN-γ) can enhance HIV replication, and peripheral blood mononuclear cells (PBMC) infected with HIV in vitro secrete high levels of the same cytokines. As T cells secrete all three mediators, the capacity of T cell activation signals to trigger cytokine production in PBMC from HIV-infected individuals was investigated as such patients may be immunocompromised. We demonstrate that asymptomatic seropositives in CDC group II/III as well as patients who have progressed to CDC group IV of the disease proliferate efficiently to anti-CD3 antibody, recombinant interleukin-2 (rIL-2), phytohaemagglutinin (PHA), PHA plus phorbol 12, 13 dibutyrate (PMA) but secrete significantly (P>0.05) higher amounts of TNF-α, TNF-β and IFN-γ compared with controls in response to the same stimulants. We also show a difference between group II/III and group IV patients with the latter secreting more TNF-α and IFN-γ. The kinetics of TNF-α and -β and IFN-γ production was stimulus dependent with overall levels varying in time for each stimulus. Furthermore, the kinetics of the response to all three stimulants were altered in seropositives; CDC group II/III and group IV patients secreted higher levels of cytokines over several time points compared to controls. The altered production of these mediators by HIV-infected patients may contribute to disease progression and to the pathogenesis of AIDS.