Effects of tumour necrosis factor alpha and melphalan on the cytokine production of circulating T cells in patients with cancer.
BACKGROUND
The objective of the present study was to investigate the effects of isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF-alpha) and melphalan on circulating T cells from cancer patients using two different methods.


METHODS
Eight patients undergoing an ILP entered the study. At first, the number of T cells at several time points was determined using FACScan. Subsequently, production of interferon gamma (IFN-gamma) (T-helper 1) and interleukin (IL) 4 (T-helper 2) was measured at the intracytoplasmic level after stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. IFN-gamma, IL-4 and IL-2 (also T-helper 1) production in the whole-blood cell culture system was then determined after stimulation with a combination of anti-CD3/anti-CD28 monoclonal antibodies.


RESULTS
An enormous decrease in the number of circulating T cells was observed. In the remaining T-cell population cytokine production (IL-2, IL-4, IFN-gamma) was depressed, showing the same pattern in both methods. No difference could be detected between the effect of TNF-alpha and melphalan on Th1 cells and Th2 cells.


CONCLUSIONS
The results demonstrate that TNF-alpha and melphalan reduce the number of circulating T cells and at the single-cell level decrease cytokine production in the remaining circulating T cells. No selective effect of TNF-alpha on Th1 or Th2 cells could be detected. If the impaired T-cell function is representative of all T cells remaining in the systemic circulation, this could help to explain the tolerability of high TNF concentrations after ILP, perhaps by decreasing the synthesis and production of T-cell-derived cytokines.
Stam
T C
TC
Department of Surgical Oncology, University Hospital Rotterdam, Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands.
Eggermont
A M
AM
Swaak
A J
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008558:Melphalan / Q000494:pharmacology*; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018906:Antineoplastic Agents, Alkylating; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan