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

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.