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In this study we analysed serum IL-2 levels in 61 patients with multiple myeloma (MM). Patients serum IL-2 levels were significantly higher than normal controls. Moreover, higher serum IL-2 levels were associated with a prolonged actuarial survival. In particular, 87% of the MM patients with IL-2 greater the or equal to 10 U/ml are still alive at 5 years while only 13% of the remaining patients with IL-2 less than 10 U/ml are alive. The multivariate analysis confirmed these data indicating that high serum IL-2 levels are the most useful predictor index of longer survival in MM patients. Furthermore, among the 50 patients in whom serum beta-2-microglobulin (SB2M) determination was available we observed that all patients with serum IL-2 levels greater than or equal to 10 U/ml had SB2M less than 6 micrograms/ml, whereas in patients with serum IL-2 less than 10 U/ml SB2M ranged from 1.3 to 15 micrograms/ml. Using these two parameters we were able to identify three groups of patients with different survival duration. Group A (9 patients) defined by serum IL-2 greater than or equal to 10 U/ml and SB2M less than 6 micrograms/ml in which all patients are alive: group B (26 patients) characterized by serum IL-2 less than 10 U/ml and SB2M less than 6 micrograms/ml in which 24% of patients are alive and group C (15 patients) characterized by serum IL-2 levels less than 10 U/ml and SB2M greater than or equal to 6 micrograms/ml in which the actuarial survival curve drops to 0 at 2.5 years. A statistically significant difference was observed between groups A and B (P less than 0.05), groups A and C (P less than 0.01) and groups B and C (P less than 0.01). These data could reflect the existence of an active T cell control on B cell neoplasia and may suggest the opportunity of a more extensive use of recombinant biological modifiers such as IL-2 in the therapeutic strategy of MM.

Interleukin-1 (IL-1), Interleukin-2 (IL-2) and soluble receptors for IL-2 (sIL-2R) play a crucial role in the immune response. IL-2 in particular is implicated not only in T-cell proliferation but also in normal B-cell proliferation and differentiation and in the development of B and T cell malignancies. We have assayed the serum levels of IL-1, IL-2 and sIL-2R in 12 patients with monoclonal gammopathy of undetermined significance (MGUS) and 44 patients with multiple myeloma (MM). Sera collected from 40 healthy blood donors were used for normal values, and sera from 33 medical volunteers over 48 years of age (median age 52 years) for normal IL-2 values in the elderly. Mean IL-2 serum values were 6.50 U/ml in MGUS and 4.97 U/ml in MM patients. There was a statistical significant elevation of IL-2 levels is both MM and MGUS patients when compared to both normal controls (p less than 0.001, Wilcoxon two tailed test). A significant difference in IL-2 levels (p less than 0.025) was also observed between MGUS and MM patients. The levels of serum IL-1 and sIL-2R were normal both in MGUS and MM patients. In 24 MM patients where the dosage of serum beta-2-microglobulin was available, a significant difference (p less than 0.01) in serum IL-2 levels was found between patients with beta-2-microglobulin greater than 6 micrograms/ml and less than 6 micrograms/ml. Pathogenic mechanisms as well as their possible clinical significance are discussed.