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Effects of tumour necrosis factor α and melphalan on the cytokine production of circulating T cells in patients with cancer
Author(s) -
T. Stam,
Alexander M.M. Eggermont,
A. J. G. Swaak
Publication year - 1999
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1999.00452.x
Subject(s) - cytokine , tumor necrosis factor alpha , immunology , melphalan , medicine , ionomycin , monoclonal antibody , population , t cell , endocrinology , stimulation , biology , antibody , immune system , multiple myeloma , environmental health
Background The objective of the present study was to investigate the effects of isolated limb perfusion (ILP) with tumour necrosis factor α (TNF‐α) and melphalan on circulating T cells from cancer patients using two different methods. Design 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‐γ) (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‐γ, 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‐γ) was depressed, showing the same pattern in both methods. No difference could be detected between the effect of TNF‐α and melphalan on Th1 cells and Th2 cells. Conclusions The results demonstrate that TNF‐α 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‐α 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.