Based on the possibility of
tumor necrosis factor (
TNF)-alpha to perform multiple and opposite
biologic effects, we simultaneously investigated in vitro its effects on intracellular
lactate dehydrogenase (
LDH)-H and
LDH-M isoenzyme activity and morphological characteristics following induction of apoptosis in peripheral blood mononuclear cells (PBMC) of
non-Hodgkin's lymphoma patients (NHL) prior to and after the end of applied
chemotherapy.
TNF-alpha showed a significant increase ( p<0.05) of
LDH-H and
LDH-M activity in sonified PBMC of healthy controls after 18 h cultures accompanied with an increase of apoptotic index (AI) from 2.3 to 16.2%. Contrary to this, in PBMC of NHL patients prior to
therapy TNF-alpha induced a significant decrease ( p<0.05) of
LDH-H isotype activity. In patients after administration of
chemotherapy,
TNF-alpha in a dose of 100 U/ml induced a significant increase ( p<0.05) of
LDH-M isotype activity, but not of
LDH-H. In the PBMC of NHL patients prior to
chemotherapy,
TNF-alpha in vitro induced an increase of AI from 2.8 up to 6.8%, while in PBMC of NHL patients after applied
chemotherapy AI changed from 7.2 to 14.4%. However, there was no significant difference in the increase of apoptosis in PBMC of NHL patients with high-grade
malignancy and high rate response among patients who received first-line
therapy, high-dose
therapy, or third-line
therapy regimens after in vitro
TNF-alpha treatment. These results indicated different susceptibilities of PBMC of NHL to
TNF-alpha when effects were analyzed by determination of intracellular LDH isotype profile and induction of apoptosis prior to and after administration of
therapy in comparison to effects on healthy controls PBMC.