Effect of ultraviolet-inducible cytokines on melanoma growth in vivo: stimulation of melanoma growth by interleukin-1 and -6.

Ultraviolet light of wavelengths 280-320 nm (UVB) can induce transcription of cytokine mRNAs and increase expression of the corresponding proteins 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). Several of these cytokines can influence the growth of tumour cells as well 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 melanoma in vivo and in vitro, using the murine B16 melanoma and its syngeneic host, the C57BL/6 mouse. Mice were injected with 0.1-1.5 micrograms of recombinant cytokine subcutaneously every other day following a subcutaneous 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 tumour growth in vivo. TNF-alpha, TGF-beta, IL-2 and IL-8 had no significant 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 size than those of the control animals. The IL-1-treated animals also showed highly vascularized tumours that invaded underlying muscle tissue more rapidly than controls. These tumors also showed a strong positive reaction with antibody to intercellular adhesion molecule-1.(ABSTRACT TRUNCATED AT 250 WORDS)