Reduced apoptosis by pentoxiphylline among patients with HIV infection

Abstract

Background: Apoptosis is a significant cause of CD4 + T cell death. Caspase 8 (FLICE) is involved in apoptosis mediated by Fas and p55 tumor necrosis factor (TNF) receptor ligation. It is also partially mediated by interleukin-1beta (IL-1β)-converting enzyme (ICE; caspase 1). We and others have shown that pentoxiphylline inhibits TNF-α. We used it among patients with HIV infection to determine if 24 weeks of therapy altered the levels of caspase 1 and caspase 8. Patients and methods: Nineteen HIV-infected patients having no opportunistic infection at the time of recruitment were administered pentoxiphylline 400 mg thrice daily for 24 weeks. Caspase levels were measured using a single-step ELISA using commercially available monoclonal antibodies against caspase 1 and caspase 8. Results: Mean CD4 counts of the patients were 202.6±111.6 (/mm 3). Mean OD value of caspase 1 among patients before therapy was 0.302±0.197 and was higher than that of controls (0.287±0.064), but this was not statistically significant. Following 24 weeks of therapy with pentoxiphylline, the OD value declined significantly to 0.164±0.028 among patients ( p<0.001). Mean OD value of caspase 8 among patients prior to therapy was 0.927±0.249. This was significantly higher than that of controls, whose level was 0.0074±0.004 ( p<0.001). Following 24 weeks of therapy with pentoxiphylline, the OD value declined to 0.199±0.064 among patients and this was significantly lower than the value at the start of treatment ( p<0.001). Conclusion: Therapy with pentoxiphylline for 24 weeks is associated with a decline in the levels of caspase 1 and caspase 8. Since the drug is known to produce TNF inhibition, this might result in reduced apoptosis and an improved CD4 lymphocyte survival.