Elevated Levels of Soluble Interleukin 2 Receptor and Tumor Necrosis Factor in Nasopharyngeal Carcinoma Mow-Ming Hsu, MD; Jenq-Yuh Ko, MD; Yen-Liang Chang, MD \s=b\ Depressed

cell-mediated immunity as a of the mitogenic response of mononuclear cells in patients with nasopharyngeal carcinoma is well documented, but the mechanism is still unclear. The enzyme-linked immunosorbent assay was used to measure soluble interleukin 2 receptor and tumor necrosis factor levels in 295 patients with nasopharyngeal carcinoma and 97 age-matched control subjects. Soluble interleukin 2 receptor levels in patients with nasopharyngeal carcinoma were elevated and correlated with clinical staging. Higher soluble interleukin 2 receptor levels were found in patients with bone metastasis but not in patients with intracranial involvement. The levels of tumor necrosis factor in nasopharyngeal carcinoma were higher than in control subjects but did not correlate with clinical staging. These data suggest that soluble interleukin 2 receptor levels might be more useful than soluble tumor necrosis factor levels that indicate tumor bulk. Soluble interleukin 2 receptor serves as a blocking factor that competes with interleukin 2 function, resulting in a decreased mitogenic response in patients with nasopharyngeal carcinoma. The usefulness of the levels of soluble interleukin 2 receptor to monitor the efficacy of treatment in patients with nasopharyngeal carcinoma with bone metastasis requires further study. (Arch Otolaryngol Head Neck Surg.

underestimated. In an attempt to im¬ prove the quality of life of patients who survive NPC by reducing the dosage of irradiation and adding immunotherapy, a series of immunologie studies have been performed in the Depart¬ ment of Otolaryngology, National Tai¬ wan University Hospital, Taipei, since 1975. Decreased blastogenesis to phytohemagglutinin, concanavalin A, or


(TNF), a macrophage hormone, was reported to be a basic factor in the



pokeweed mitogen

generally found in NPC, even in the early stages of the disease,2,3 but the reason is still unclear. Although the normal response was

to interleukin 2

(IL-2) stimulation was elicited in mononuclear cells in NPC, a decreased concentration of IL-2 was found. An additional study of IL-2 production revealed a similarity be¬ tween patients with NPC and control subjects. Increased IL-2 consumption in NPC was speculated.4 Soluble IL-2 receptor (sIL-2R) was demonstrated in T-cell activation and was able to compete for binding IL-2.5 Elevated sIL-2R levels were a sensitive tumor marker in animals bearing the aggres¬ sive tumor.6 The serum levels of sIL2R were proved to be a reliable mark¬ er of neoplastic bulk in hairy-cell leukemia.' Tumor necrosis factor

carcinoma (NPC) is one of the common cancers encountered in Taiwan. The treatment of choice for NPC is high-dose irradia¬ tion with or without chemotherapy. Although the overall 5-year survival was recently reported to be 70%/ the side effects of irradiation should not be

mechanism of cachexia.8 Because a quarter of patients with NPC died of cachexia,9 TNF might be important in the course of NPC. This is a prelimi¬ nary report on the study of sIL-2R and TNF levels in patients with NPC.

Accepted for publication July 31,1991. From the Department of Otolaryngology, College of Medicine, National Taiwan University, Taipei. Read before the American Society for Head and Neck Surgery, Waikaloa, Hawaii, May 9,1991. Reprint requests to the Department of Otolaryngology, National Taiwan University Hospital, No. 1 Chang-Te St, Taipei, Taiwan (Dr Hsu).

A total of 295 patients (219 men and 76 women) with pathologically verified NPC were studied. Their mean age was 45.5 years (range, 18 to 76 years). Clinical staging was determined according to our criteria. Brief¬ ly, in stage I disease, the primary tumor was confined to the nasopharynx without cervical



involvement; in stage II disease, the primary tumor was as described in stage I disease and extended into the nasal cavity or oropharynx or involved the skull base, with or without mobile upper cervical nodes; in stage III disease, the primary tumor was as described in stage II disease, with cranial nerve involvement, direct extension to the hypopharynx, or involvement of upper and lower cervical nodes; and in stage IV disease, node

intracranial involvement, fixed cervical nodes, and/or distant metastasis were pre¬ sent. The control group included 97 subjects who were age-matched from the group of patients admitted for elective surgery of the ear or nose or from among medical personnel.

Determination of slL-2R and TNF Levels The level of sIL-2R was measured with a sandwich enzyme-linked immunosorbent as¬ say (CELLFREE Interleukin-2 Receptor Test Kit, T-cell Sciences Ine, Cambridge, Mass). Briefly, a mouse monoclonal antibody to human IL-2 receptor was first absorbed onto a polystyrene microtiter well. A studied sample or standard was added to the anti¬ body-coated well, and unreacted sample components were removed by washing. A second horseradish peroxidase-conjugated murine monoclonal antibody to human IL-2 receptor was then used to bind a second epitope to the molecule captured by the first antibody. After removal of unbound enzymeconjugated anti-IL-2 receptor by washing, a substrate solution was added to the well. After the reaction was terminated by a stop solution, the absorbance at 490 nm was mea¬ sured. The mean value of absorbance from duplicate samples was then plotted on a stan¬ dard curve and converted to a numerical val¬ ue. The sIL-2R level is expressed in units per milliliter. A reference preparation of 1000 U/mL of supernatant from phytohemagglutinin-stimulated peripheral blood lymphocytes was used as a standard. The TNF level was measured similarly with the enzyme-linked immunosorbent assay (BIOKINE TNF Test Kit, T-cell Sciences Ine). The TNF level is expressed in picograms per milliliter. A reference preparation of 1000 pg lyophilized recombinant human TNF was used as a standard.

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Statistical Analysis

Table 1.- -Soluble Interleukin 2 Receptor Levels in Various Carcinoma and Controls*

The correlation coefficient and t test analyses were used to determine the correla¬ tion between sIL-2R or TNF level and clini¬ cal staging. The significance of the difference was evaluated with a t test.

Stage I 355 ± 30 (n








450 ± 29


528 (n




767 ± 74

± 56


Stages of Nasopharyngeal





Total 525 ± 24







396 ± 26


(n Values

mean ± SEM levels of sIL-2R 525 ±24 U/mL in patients with NPC (n 295) and 396 ±26 U/mL in age-matched control subjects (n 97) (Table 1). The difference was statisti¬ cally significant (P .003). The levels of sIL-2R in patients with NPC ap¬ peared to correlate with clinical stag¬ ing (r=.27, £ 4.8, P

Elevated levels of soluble interleukin 2 receptor and tumor necrosis factor in nasopharyngeal carcinoma.

Depressed cell-mediated immunity as a measure of the mitogenic response of mononuclear cells in patients with nasopharyngeal carcinoma is well documen...
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