RELATIONSHIP BETWEEN SOLUBLE TUMOR-NECROSIS-FACTOR (TNF) RECEPTORS AND TNF-ALPHA DURING IMMUNOTHERAPY WITH INTERLEUKIN-2 AND OR INTERFERON-ALPHA/

Eleven metastatic cancer patients were studied during three different regimens of immunotherapy with interleukin-2 (IL-2) and/or interferon alpha (IFN alpha): group A received 4 days of IL-2 i. a. infusion (n = 3), group B IFN alpha s.c. during 5 days (n = 4), followed on day 3 b y 5 days of a continuous IL-2 i.v. infusion, and group C had 4 days of IL-2 i.v. infusion together with s.c. IFN alpha on days 1 and 4 (n = 4). Soluble tumor necrosis factor receptors (sTNFR) p55 and p75 and TN F alpha concentrations in serum were analyzed before therapy and daily during 8 days of the first therapy cycle. sTNFR was measured by radio immunoassay, sTNFR p55 increased in all patient groups from a baseline value of 5.2 +/- 0.9 ng/ml to a maximum of 13.6 +/- 1.2 ng/ml by days 3-4 (P = 0.003). sTNFR p75 increased from 7.6 +/- 1.1 ng/ml to peak v alues of 30.1 +/- 2.6 ng/ml in groups A and B (P = 0.02). In group C t he sTNFR p75 response was weak (NS). In group B, the increase of both p55 and p75 occurred only after addition of IL-2 to IFN alpha. TNF alp ha increased weakly during treatment with IFN alpha alone (group B); i t rose strongly during IL-2 and the combined treatment (groups A-C) fr om 8 +/- 2 pg/ml to 115 +/- 13 pg/ mi (P = 0.003). In group B, it reac hed the maximum 24 h after addition of IL-2 to IFN alpha and decreased thereafter. There was a significant relationship between TNF alpha an d sTNFR p55 or sTNFR p75 in groups A and C, (P = 0.001), but not in gr oup B. Group C was also investigated during the third therapy cycle. T he increase of sTNFR p75 was stronger (P = 0.01) and that of TNF alpha weaker than in the first cycle; the sTNFR p55 response was similar in both cycles. In conclusion sTNFR p55 and p75 are rapidly induced duri ng IL-2 and IL-2+ IFN alpha treatment, the increase of sTNF receptors parallels or exceeds that of TNF alpha and may influence the immunomod ulatory effects of TNF alpha during cytokine therapy.