Superiority of the ear pinna over a subcutaneous tumour inoculation site for induction of a Th1-type cytokine response

This study examines whether a correlation may be found between Th1- or Th2-type cytokine responses and resistance or susceptibility to tumour growth. Cytokine profiles were investigated in a well-defined mouse tumour model in which the injection site and the genetic background determine the phenotype of either tumour resisrance or tumour susceptibility. DBA/2-derived ESb lymphoma variant cells with high metastatic capacity were inoculated into syngeneic mice either s.c., where they grow and metastasize, or into the ear pinna (i.e.), where they do not grow because of induction of protective immunity. Alternatively, the tumour cells were injected s.c. or i.e. into allogeneic B10.D2 mice, which are resistant to the tumour although they are identical at the MHC locus. Between 1 and 10 days after tumour cell injection the spleen-derived mRNA was tested for cytokine gene expression or the spleen cells were analysed by FACScan for T cell activation. The strongest cytokine response was observed in i.e. inoculated B10.D2 mice. This was characterized by an early (days 2-3) peak of interferon gamma (INF-gamma), interleukin-2 (IL-2), IL-2 receptor alpha (IL-2R alpha) and IL-4. The cytokine mRNA response of i.e. inoculated DBA/2 mice was quite similar except that no IFN-gamma could be detected. In s.c, inoculated B10.D2 mice, the IL-2, IL-2R alpha and IFN-gamma responses were weaker than after i.e. injection while the IL-4 response was comparable. The most striking difference between these cytokine profiles from tumour-resistant mice and those of s.c. inoculated tumour-susceptible DBA/2 mice was a delay in the latter in the IL-2, IL-2R alpha and IFN-gamma responses and the observation that the IL-4 response was not down-regulated. The persisting IL-4 response could clown-regulate a Th1-type response and thereby explain tumour susceptibility as a consequence of host conditioning.