Relation of pro- and anti-inflammatory cytokines and the production of nitric oxide in patients receiving high-dose immunotherapy with interleukin-2

Immunotherapy with intravenous recombinant human interleukin-2 (rh IL-2) ma y be accompanied by hypotension and the emergence of capillary leak syndrom e. Nitric oxide (NO) is supposed to be responsible for both side effects. T he aim of the current investigation was to elucidate the relationship betwe en pro- and anti-inflammatory cytokines and the production of NO in eight t umor patients receiving intravenous rh IL-2 continuously over a time period of 120 hours. Markers of systemic inflammation, as well as nitrate plasma levels, were consecutively determined. Significant changes in the levels of pro-inflammatory cytokines IL-6 and IL-8 were observed (p < 0.05). In cont rast to the anti-inflammatory cytokine IL-10, which did not increase signif icantly, the serum concentrations of the soluble tumor necrosis factor rece ptors (sTNFr) I and II rose continuously and significantly during the obser vation period (p < 0.05). In parallel, a significant rise in nitrate plasma levels was observed (p < 0.05). Moreover, there were highly significant co rrelations between nitrate and IL-6 serum levels (p < 0.05), nitrate and sT NFr-I (p < 0.05), nitrate and sTNFr-II (p < 0.05), and between IL-6 and IL- 10 (p < 0.05), respectively. We conclude that immunotherapy with IL-2 promo tes a pro-inflammatory state, parallelled by an increased production of nit ric oxide. Although anti-inflammatory responses accompany this process, the y are not able to diminish the production of nitric oxide.