EFFECT OF ULTRAVIOLET-INDUCIBLE CYTOKINES ON MELANOMA GROWTH IN-VIVO - STIMULATION OF MELANOMA GROWTH BY INTERLEUKIN-1 AND INTERLEUKIN-6

Ultraviolet light of wavelengths 280-320 nm (UVB) can induce transcrip tion of cytokine mRNAs and increase expression of the corresponding pr oteins in the epidermis. In particular, UVB can stimulate keratinocyte synthesis of interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor- alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). Seve ral of these cytokines can influence the growth of tumour cells as wel l as the host response to these tumours. In this study we examined the effect of IL-1, IL-6, IL-8, TNF-alpha and TGF-beta on the growth of m elanoma in vivo and in vitro, using the murine B16 melanoma and its sy ngeneic host, the C57BL/6 mouse. Mice were injected with 0.1-1.5 mug o f recombinant cytokine subcutaneously every other day following a subc utaneous injection of 1 X 10(5) B16 cells (F-10 clone). In this model, tumours appeared within 12-14 days, and IL-1 and IL-6 stimulated tumo ur growth in vivo. TNF-alpha, TGF-beta, IL-2 and IL-8 had no significa nt effect. In contrast to the in vivo effects, TNF-alpha inhibited B16 cell growth in vitro and IL-6 stimulated B16 cell growth. The in vivo IL-1 effect on tumour growth in mice was examined in greater detail. IL-1-treated animals showed tumours approximately 5-fold greater in si ze than those of the control animals. The IL-1-treated animals also sh owed highly vascularized tumours that invaded underlying muscle tissue more rapidly than controls. These tumors also showed a strong positiv e reaction with antibody to intercellular adhesion molecule-1. When cy tokines were administered after the injected B16 cells had formed visi ble tumours, no stimulatory effect of the cytokines was noted. These r esults suggest that UVB-inducible cytokines may be important in promot ing the seeding of tumour cells, possibly by adhesion molecule inducti on, and in regulation of the early growth and attachment phases of nas cent tumours.