INTERLEUKIN-1 RECEPTOR ANTAGONIST INHIBITS SUBCUTANEOUS B16 MELANOMA GROWTH IN-VIVO

Background: Previously we demonstrated that injection of Interleukin-a lpha (IL-1) stimulated B16 melanoma tumour growth in vivo, associated with increased intercellular adhesion molecule-1 (ICAM-1) expression o n the tumour cells (Photodermatol Photoimmunol Photomed 1994; 10: 74-7 9,). Methods: In the present study, we examined the effect of blocking IL-1 receptors - by addition of recombinant Interleukin-1 receptor an tagonist (IL-1RA) - on melanoma tumour growth in vivo and in vitro. Re sults: Subcutaneous co-injection of IL-1RA with B16 tumour cells into C57BL/6 mice, followed by injection of IL-1RA every second day reduced tumour growth significantly from day 18 to day 33 post-injection. Tre atment with IL-1RA appeared to have a bi-phasic effect, low doses bein g more effective than doses >1 mu g/mouse. After 33 days, mice treated with 1.0 or 0.1 mu g/2nd day had significantly smaller tumours than c ontrols (p<0.05), however, mice treated with 10 mu g had tumours no di fferent in size from those of untreated controls. However, survival of 1L-RA-treated mice was not significantly different between treatment groups. Addition of IL-1RA to B16 cultures in vitro caused a small dos e-dependent decrease in cell growth. Maximum inhibition (64% of contro l cell numbers) was observed after 48h in media containing greater tha n or equal to 10 ng/ml IL-1RA (p<0.05). Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), we examined the exp ression of ICAM-1 message in B16 cells treated in culture with 10 mg/m l IL-1RA or 10 ng/ml IL-1 alpha for 6h or 24h. In IL-1-treated culture s ICAM-1 mRNA expression was increased to 161% of control levels. Afte r 24h, ICAM-1 message was 198% control levels (p=0.0008). Treatment wi th IL-1RA reduced the constitute ICAM-1 expression to 75% of basal aft er 6h and to 68% of basal after 24h 9 (p=0.011). Conclusion: Abrogatio n of IL-1 activity, in combination with other systemic therapies may p rove useful in ther treatment of melanoma.