The influence of oxygen and carbon dioxide tension on the production of TNF alpha by activated macrophages.

The influence of oxygen tension and carbon dioxide levels on human TNF alpha (hTNF alpha) production by the monocyte/macrophage cell line U937 has been examined. The cells were stimulated under different oxygen and carbon dioxide concentrations in the presence and absence of the known TNF alpha inducer phorbol 12-myristate 13-acetate (PMA). The results indicated that U937 cells stimulated with PMA produced up to 10 times more TNF alpha when incubated under tumour-relevant oxygen tensions of 1% rather than under aerobic conditions, i.e. 21% O2. Increasing the carbon dioxide levels from 5% to 7% however decreased the amount of PMA-stimulated hTNF alpha produced. No hTNF alpha was produced in the unstimulated U937 cells, indicating that low oxygen tensions (hypoxia) alone did not induce the production of TNF alpha, in this case.