Reduced apoptosis by pentoxiphylline among patients with HIV infection.
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-1beta)-converting enzyme (ICE; caspase 1). We and others have shown that pentoxiphylline inhibits TNF-alpha. We used it among patients with HIV infection to determine if 24 weeks of therapy altered the levels of caspase 1 and caspase 8.


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).


CONCLUSIONS
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.
Wanchu
A
A
Department of Internal Medicine, Post-Graduate Institute of Medical Education and Research, Chandigarh 160012, India. awanchu@glide.net.in
Bhatnagar
A
A
Kumar
B
B
Bambery
P
P
Singh
S
S
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D018791:CD4 Lymphocyte Count; D020170:Caspase 1 / Q000378:metabolism; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D014409:Tumor Necrosis Factor-alpha; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1; D010431:Pentoxifylline