title: Relationship between soluble tumor necrosis factor (TNF) receptors and TNF alpha during immunotherapy with interleukin-2 and/or interferon alpha.
abstract: 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 by 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 TNF alpha concentrations in serum were analyzed before therapy and daily during 8 days of the first therapy cycle. sTNFR was measured by radioimmunoassay. 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 values of 30.1 +/- 2.6 ng/ml in groups A and B (P = 0.02). In group C the 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 alpha increased weakly during treatment with IFN alpha alone (group B); it rose strongly during IL-2 and the combined treatment (groups A-C) from 8 +/- 2 pg/ml to 115 +/- 13 pg/ml (P = 0.003). In group B, it reached the maximum 24 h after addition of IL-2 to IFN alpha and decreased thereafter. There was a significant relationship between TNF alpha and sTNFR p55 or sTNFR p75 in groups A and C, (P = 0.001), but not in group B. Group C was also investigated during the third therapy cycle. The 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 during IL-2 and IL-2+ IFN alpha treatment, the increase of sTNF receptors parallels or exceeds that of TNF alpha and may influence the immunomodulatory effects of TNF alpha during cytokine therapy.
authors.affiliation: Department of Research and Internal Medicine, University Hospital, Basel, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Landmann
authors.forename: U
authors.initials: U
authors.lastname: Keilholz
authors.forename: C
authors.initials: C
authors.lastname: Scheibenbogen
authors.forename: M
authors.initials: M
authors.lastname: Brockhaus
authors.forename: H
authors.initials: H
authors.lastname: Gallati
authors.forename: H
authors.initials: H
authors.lastname: Denz
authors.forename: M
authors.initials: M
authors.lastname: Bargetzi
authors.forename: C
authors.initials: C
authors.lastname: Ludwig
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy; D012995:Solubility; D013964:Thyroid Neoplasms / Q000097:blood / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016898:Interferon-alpha; D007376:Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha