TNF-alpha reverses the disease-exacerbating effect of subcutaneous immunization against murine cutaneous leishmaniasis.

Earlier studies have demonstrated that mice injected subcutaneously or intramuscularly with leishmanial antigens develop significantly exacerbated disease compared with unimmunized controls when challenged with the cutaneous protozoan parasites Leishmania major. We report here that this disease enhancement can be prevented, and protective immunity induced, by the incorporation of recombinant tumour necrosis factor (TNF-alpha) in the immunizing inoculum. This effect of TNF-alpha is dose-dependent and is not evident when TNF-alpha and the antigens are injected into separate sites. Furthermore, TNF-alpha injected together with p183, a peptide known to preferentially stimulate Th2 cells and disease exacerbation in H-2d mice, activates spleen and lymph node cells secreting more interferon-gamma (IFN-gamma) and less interleukin-4 (IL-4) and induces a modest but significant degree of resistance against L. major infection in highly susceptible BALB/c mice.